Revision as of 03:16, 8 November 2019

Page editor		Section editor
	Ivy Abraham, MD University of Illinois at Chicago Chicago, IL		Neeta K. Venepalli, MD, MBA University of Illinois at Chicago Chicago, IL

Note: there is significant overlap between regimens for gastric cancer and esophageal cancer, if you can't find the regimen you're looking for here, please try the esophageal cancer page. If you still can't find it, it is possible that we've moved it to the historical regimens page.

71 regimens on this page 108 variants on this page

Guidelines

CAP/ASCP/ASCO

2017: Bartley et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma PubMed

ESMO

2016: Smyth et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

ESMO/ESSO/ESTRO

2013: Waddell et al. Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

NCCN

NCCN Guidelines - Gastric Cancer

Neoadjuvant chemotherapy

Cisplatin & Fluorouracil

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FP: Fluorouracil & Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Efficacy
Ychou et al. 2011 (ACCORD 07)	Phase III (E)	Surgery alone	Seems to have superior OS

This is the neoadjuvant portion of pre-planned "perioperative" therapy.

Study included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 60 minutes once on day 1
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

28-day cycle for 2 to 3 cycles

Subsequent treatment

Surgical resection, then adjuvant cisplatin & 5-FU

References

ACCORD 07: Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. link to original article contains protocol PubMed

ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2006 (MAGIC)	Phase III (E)	Surgery alone	Superior OS
Cats et al. 2018 (CRITICS)	Non-randomized portion of RCT

This is the neoadjuvant portion of pre-planned perioperative therapy. In CRITICS, only patients with difficulties swallowing tablets were assigned to this treatment.

CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction

MAGIC included patients with lower esophageal malignancy as well (74% gastric, 14.8% lower esophagus, and 11.2% GE junction).

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m²)

Supportive medications

MAGIC, suggested as thrombosis prophylaxis:
- Warfarin (Coumadin) 1 mg PO once per day

21-day cycle for 3 cycles

Subsequent treatment

MAGIC: Surgical resection is performed 3 to 6 weeks after the completion of cycle 3, followed in 6 to 12 weeks by adjuvant ECF
CRITICS: Surgery with a D1+ lymph node resection, then adjuvant ECF versus capecitabine, cisplatin, RT

References

MAGIC: Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains protocol PubMed
CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains verified protocol PubMed

ECX

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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)

Regimen

Study	Evidence
Cats et al. 2018 (CRITICS)	Non-randomized portion of RCT

CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 3 cycles

Subsequent treatment

Surgery with a D1+ lymph node resection, then adjuvant ECX versus capecitabine, cisplatin, RT

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains verified protocol PubMed

EOF

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EOF: Epirubicin, Oxaliplatin, Fluourouracil

Regimen

Study	Evidence
Cats et al. 2018 (CRITICS)	Non-randomized portion of RCT

CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m²)

21-day cycle for 3 cycles

Subsequent treatment

Surgery with a D1+ lymph node resection, then adjuvant EOF versus capecitabine, cisplatin, RT

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains verified protocol PubMed

EOX

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EOX: Epirubicin, Oxaliplatin, Xeloda (Capecitabine)

Regimen

Study	Evidence
Cats et al. 2018 (CRITICS)	Non-randomized portion of RCT

CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1
Capecitabine (Xeloda) 625 mg/m² PO twice per day

21-day cycle for 3 cycles

Subsequent treatment

Surgery with a D1+ lymph node resection, then adjuvant EOX versus capecitabine, cisplatin, RT

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains verified protocol PubMed

FLOT

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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)

Regimen

Study	Evidence	Comparator	Efficacy
Al-Batran et al. 2016 (FLOT4-AIO)	Phase II/III (E)	ECF/ECX See link	Seems to have superior OS See link

This is the neoadjuvant portion of pre-planned perioperative chemotherapy.

Chemotherapy

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours on day 1
Folinic acid (Leucovorin) 200 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 85 mg/m² IV once on day 1
Docetaxel (Taxotere) 50 mg/m² IV once on day 1

14-day cycle for 4 cycles

Subsequent treatment

Surgery, then adjuvant FLOT

References

FLOT4-AIO: Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. link to original article PubMed
1. Update: Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 Apr 10. [Epub ahead of print] link to original article PubMed

No neoadjuvant therapy

Regimen

Study	Evidence	Comparator	Efficacy
Schuhmacher et al. 2010 (EORTC 40954)	Phase III (C)	Cisplatin, 5-FU, Folinic acid	Seems not superior

No antineoplastic treatment prior to surgery.

Subsequent treatment

Surgery

References

EORTC 40954: Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010 Dec 10;28(35):5210-8. Epub 2010 Nov 8. link to original article link to PMC article PubMed

Adjuvant therapy

CapeOx

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CapeOX: Capecitabine & OXaliplatin

Regimen

Study	Evidence	Comparator	Efficacy
Bang et al. 2012 (CLASSIC)	Phase III (E)	Surgery alone	Superior OS (*)

Note: Reported efficacy is based on the 2014 update.

Preceding treatment

Gastrectomy with D2 dissection

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1

21-day cycle for 8 cycles

References

CLASSIC: Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH; CLASSIC trial investigators. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012 Jan 28;379(9813):315-21. Epub 2012 Jan 7. link to original article contains protocol PubMed
1. Update: Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ; CLASSIC trial investigators. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1389-96. Epub 2014 Oct 15. link to original article PubMed

Carboplatin & Docetaxel

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Regimen

Study	Evidence	Comparator	Efficacy
Bamias et al. 2010	Phase III (C)	Carboplatin, Docetaxel, RT	Seems not superior

Note: the original protocol was for cisplatin & docetaxel but was changed due to excess CINV. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Preceding treatment

Surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycle for 6 cycles

References

Bamias A, Karina M, Papakostas P, Kostopoulos I, Bobos M, Vourli G, Samantas E, Christodoulou Ch, Pentheroudakis G, Pectasides D, Dimopoulos MA, Fountzilas G. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010 May;65(6):1009-21. Epub 2010 Feb 4. link to original article contains protocol PubMed

Cisplatin & Fluorouracil

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Regimen

Study	Evidence	Comparator	Efficacy
Ychou et al. 2011 (ACCORD 07)	Phase III (E)	Surgery alone	Seems to have superior OS

This is the adjuvant portion of pre-planned "perioperative" therapy.

Study included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).

Preceding treatment

Neoadjuvant cisplatin & 5-FU, then surgery

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 60 minutes once on day 28
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

28-day cycle for 3 to 4 cycles, for a total of 6 cycles

References

ACCORD 07: Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. link to original article contains protocol PubMed

CX

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CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Efficacy
Lee et al. 2011 (ARTIST_gastric)	Phase III (C)	XP, then RT, then XP	Might have inferior DFS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm. This trial should not be confused for the one by the same name in colorectal cancer.

Preceding treatment

R0 gastrectomy and at least D2 dissection

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 6 cycles

References

ARTIST: Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. Epub 2011 Dec 19. link to original article contains verified protocol PubMed
1. Update: Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: Final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. Epub 2015 Jan 5. link to original article PubMed

ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2006 (MAGIC)	Phase III (E)	Surgery alone	Superior OS
Cats et al. 2018 (CRITICS)	Phase III (C)	CX & RT	Seems not superior

This is the adjuvant portion of pre-planned "perioperative" therapy. In CRITICS, only patients with trouble swallowing pills were assigned to this treatment arm.

MAGIC included patients with lower esophageal malignancy (74% gastric, 14.8% lower esophagus, and 11.2% GE junction).

Preceding treatment

Neoadjuvant ECF x 3, then surgery

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m²)

Supportive medications

MAGIC, suggested as thrombosis prophylaxis:
- Warfarin (Coumadin) 1 mg PO once per day

21-day cycle for 3 cycles

References

MAGIC: Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains protocol PubMed
CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains verified protocol PubMed

ECX

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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)

Regimen

Study	Evidence	Comparator	Efficacy
Cats et al. 2018 (CRITICS)	Phase III (C)	CX & RT	Seems not superior

Preceding treatment

ECX x 3, then surgery

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 3 cycles

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains verified protocol PubMed

EOF

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EOF: Epirubicin, Oxaliplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Cats et al. 2018 (CRITICS)	Phase III (C)	CX & RT	Seems not superior

Only patients with trouble swallowing pills were assigned to this treatment arm.

Preceding treatment

EOF x 3, then surgery

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m²)

21-day cycle for 3 cycles

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains verified protocol PubMed

EOX

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EOX: Epirubicin, Oxaliplatin, Xeloda (Capecitabine)

Regimen

Study	Evidence	Comparator	Efficacy
Cats et al. 2018 (CRITICS)	Phase III (C)	CX & RT	Seems not superior

Preceding treatment

EOX x 3, then surgery

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1
Capecitabine (Xeloda) 625 mg/m² PO twice per day

21-day cycle for 3 cycles

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains verified protocol PubMed

FLOT

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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)

Regimen

Study	Evidence	Comparator	Efficacy
Al-Batran et al. 2016 (FLOT4-AIO)	Phase II/III (E)	ECF/ECX See link	Seems to have superior OS See link

This is the adjuvant portion of pre-planned perioperative chemotherapy.

Preceding treatment

Neoadjuvant FLOT x 4, then surgery

Chemotherapy

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours on day 1
Folinic acid (Leucovorin) 200 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 85 mg/m² IV once on day 1
Docetaxel (Taxotere) 50 mg/m² IV once on day 1

14-day cycle for 4 cycles

References

FLOT4-AIO: Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. link to original article PubMed
1. Update: Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 Apr 10. [Epub ahead of print] link to original article PubMed

FP/Capecitabine & RT

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FP/Capecitabine & RT: Fluorouracil & Platinol (Cisplatin) alternating with Capecitabine & Radiation Therapy

Regimen

Study	Evidence
Lee et al. 2006	Phase II

Note: In contrast to the primary reference, some guidelines list this regimen without FP cycles 1, 3, 4, 5. Dosage of Capecitabine (Xeloda) was listed as 625 to 825 mg/m² PO twice per day on days 1 to 5 or 1 to 7 while radiation is being given.

Preceding treatment

Surgery, 3 weeks prior

Chemotherapy, part 1

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose: 5000 mg/m²)

21-day cycle, followed immediately by:

Chemotherapy, part 2

Capecitabine (Xeloda) 825 mg/m² PO twice per day

Radiotherapy

Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions (total dose of 45 Gy)

5-week course, followed 4 weeks later by:

Chemotherapy, part 3

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m²)

21-day cycle for 3 cycles

References

Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH, Kim JS, Lee JH, Jung GJ, Kim MC. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol. 2006 Jan 28;12(4):603-7. link to original article contains verified protocol link to PMC article PubMed

FULV/FULV & RT

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FULV/FULV & RT: FluoroUracil & LeucoVorin (Folinic acid) alternating with FluoroUracil, LeucoVorin (Folinic acid) & Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Macdonald et al. 2001 (INT-0116)	Phase III (E)	Surgery alone	Superior OS
Fuchs et al. 2017 (CALGB 80101)	Phase III (C)	ECF, then FULV & RT, then ECF	Seems not superior

Treatment is to start 20 to 40 days after surgery.

Study included patients with GE junction malignancy as well (20% GE junction) and included patients with a performance status of 2.

Preceding treatment

INT-0116: Surgery with R0 resection (10% underwent D2 dissection, 36% underwent D1 dissection and 54% underwent D0 dissection)
CALGB 80101: Surgery

Chemotherapy, part 1

Fluorouracil (5-FU) 425 mg/m² IV bolus once per day on days 1 to 5
Folinic acid (Leucovorin) 20 mg/m² IV bolus once per day on days 1 to 5

28-day cycle for 1 cycle, followed by:

Chemotherapy, part 2

Fluorouracil (5-FU) 400 mg/m² IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
Folinic acid (Leucovorin) 20 mg/m² IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy

Radiotherapy

Concurrent radiation therapy 180 cGy x 25 fractions (total of 45 Gy)

35-day course, followed in 1 month by:

Chemotherapy, part 3

Fluorouracil (5-FU) 425 mg/m² IV bolus once per day on days 1 to 5
Folinic acid (Leucovorin) 20 mg/m² IV bolus once per day on days 1 to 5

28-day cycle for 2 cycles

References

INT-0116: Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. link to original article contains protocol PubMed
1. Update: Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. link to original article link to PMC article PubMed
CALGB 80101: Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, Enzinger PC, Haller DG, Dragovich T, Alberts SR, Bjarnason GA, Willett CG, Gunderson LL, Goldberg RM, Venook AP, Ilson D, O'Reilly E, Ciombor K, Berg DJ, Meyerhardt J, Mayer RJ. Adjuvant chemoradiotherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: results from CALGB 80101 (Alliance). J Clin Oncol. 2017 Nov 10;35(32):3671-3677. Epub 2017 Oct 4. link to original article contains verified protocol link to PMC article PubMed

Observation

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Regimen

Study	Evidence	Comparator	Efficacy
Allum et al. 1989	Phase III (C)	5-FU & Mitomycin	Seems not superior
Coombes et al. 1990	Phase III (C)	FAM	Seems not superior
Hallissey et al. 1994	Phase III (C)	1. FAM 2. Radiation therapy	Seems not superior
Lise et al. 1995 (EORTC 40813)	Phase III (C)	FAM2	Might have inferior DFS
Macdonald et al. 1995	Phase III (C)	FAM	Seems not superior
Nakajima et al. 1999 (JCOG8801)	Phase III (C)	5-FU & Mitomycin, then UFT	Seems not superior
Cirera et al. 1999	Phase III (C)	Mitomycin & Tegafur	Seems to have inferior OS
Macdonald et al. 2001 (INT-0116)	Phase III (C)	FULV/FULV & RT	Inferior OS
Nashimoto et al. 2003 (JCOG 9206-1)	Phase III (C)	5-FU, Ara-C, Mitomycin, then 5-FU	Seems not superior
Bouché et al. 2005 (FFCD 8801)	Phase III (C)	Cisplatin & 5-FU	Seems not superior
Nitti et al. 2005	Phase III (C)	1. FAMTX 2. FEMTX	Seems not superior
Cunningham et al. 2006 (MAGIC)	Phase III (C)	ECF	Inferior OS
De Vita et al. 2007 (GOIM 9602)	Phase III (C)	ELFE	Seems not superior
Sakuramoto et al. 2007 (ACTS-GC)	Phase III (C)	S-1	Inferior OS
Di Costanzo et al. 2008	Phase III (C)	PELF	Seems not superior
Kulig et al. 2010	Phase III (C)	EAP	Seems not superior
Miyashiro et al. 2011 (JCOG 9206-2)	Phase III (C)	IV/IP Cisplatin, then UFT	Seems not superior

No further treatment after surgery.

Preceding treatment

Surgery, with varying requirements for level of dissection (see papers for details)

References

Allum WH, Hallissey MT, Kelly KA; British Stomach Cancer Group. Adjuvant chemotherapy in operable gastric cancer: 5 year follow-up of first British Stomach Cancer Group trial. Lancet. 1989 Mar 18;1(8638):571-4. link to original article PubMed
Coombes RC, Schein PS, Chilvers CE, Wils J, Beretta G, Bliss JM, Rutten A, Amadori D, Cortes-Funes H, Villar-Grimalt A, McArdle C, Rauschecker HF, Boven E, Vassilopoulos P, Welvaart K, Pinto Ferreira E, Wiig J, Gisselbrecht C, Rougier P, Woods EMA; International Collaborative Cancer Group. A randomized trial comparing adjuvant fluorouracil, doxorubicin, and mitomycin with no treatment in operable gastric cancer. J Clin Oncol. 1990 Aug;8(8):1362-9. link to original article PubMed
Hallissey MT, Dunn JA, Ward LC, Allum WH; British Stomach Cancer Group. The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up. Lancet. 1994 May 28;343(8909):1309-12. link to original article PubMed
EORTC 40813: Lise M, Nitti D, Marchet A, Sahmoud T, Buyse M, Duez N, Fiorentino M, Dos Santos JG, Labianca R, Rougier P, Gignoux M. Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer. J Clin Oncol. 1995 Nov;13(11):2757-63. link to original article PubMed
Macdonald JS, Fleming TR, Peterson RF, Berenberg JL, McClure S, Chapman RA, Eyre HJ, Solanki D, Cruz AB Jr, Gagliano R, Estes NC, Tangen CM, Rivkin S. Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A Southwest Oncology Group study. Ann Surg Oncol. 1995 Nov;2(6):488-94. link to original article PubMed
JCOG8801: Nakajima T, Nashimoto A, Kitamura M, Kito T, Iwanaga T, Okabayashi K, Goto M; Gastric Cancer Surgical Study Group. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Lancet. 1999 Jul 24;354(9175):273-7. link to original article PubMed
Cirera L, Balil A, Batiste-Alentorn E, Tusquets I, Cardona T, Arcusa A, Jolis L, Saigí E, Guasch I, Badia A, Boleda M. Randomized clinical trial of adjuvant mitomycin plus tegafur in patients with resected stage III gastric cancer. J Clin Oncol. 1999 Dec;17(12):3810-5. link to original article PubMed
INT-0116: Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. link to original article contains protocol PubMed
1. Update: Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. link to original article link to PMC article PubMed
JCOG 9206-1: Nashimoto A, Nakajima T, Furukawa H, Kitamura M, Kinoshita T, Yamamura Y, Sasako M, Kunii Y, Motohashi H, Yamamoto S; Gastric Cancer Surgical Study Group, Japan Clinical Oncology Group. Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1. J Clin Oncol. 2003 Jun 15;21(12):2282-7. link to original article PubMed
FFCD 8801: Bouché O, Ychou M, Burtin P, Bedenne L, Ducreux M, Lebreton G, Baulieux J, Nordlinger B, Martin C, Seitz JF, Tigaud JM, Echinard E, Stremsdoerfer N, Milan C, Rougier P; Fédération Francophone de Cancérologie Digestive Group. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol. 2005 Sep;16(9):1488-97. Epub 2005 Jun 6. link to original article PubMed
Nitti D, Wils J, Dos Santos JG, Fountzilas G, Conte PF, Sava C, Tres A, Coombes RC, Crivellari D, Marchet A, Sanchez E, Bliss JM, Homewood J, Couvreur ML, Hall E, Baron B, Woods E, Emson M, Van Cutsem E, Lise M; EORTC GI Group; ICCG. Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer: a combined analysis of the EORTC GI Group and the ICCG. Ann Oncol. 2006 Feb;17(2):262-9. Epub 2005 Nov 17. link to original article PubMed
MAGIC: Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains protocol PubMed
GOIM 9602: De Vita F, Giuliani F, Orditura M, Maiello E, Galizia G, Di Martino N, Montemurro F, Cartenì G, Manzione L, Romito S, Gebbia V, Ciardiello F, Catalano G, Colucci G; Gruppo Oncologico Italia Meridionale. Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study). Ann Oncol. 2007 Aug;18(8):1354-8. Epub 2007 May 24. link to original article PubMed
ACTS-GC: Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. link to original article contains verified protocol PubMed
1. Update: Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. link to original article PubMed
Di Costanzo F, Gasperoni S, Manzione L, Bisagni G, Labianca R, Bravi S, Cortesi E, Carlini P, Bracci R, Tomao S, Messerini L, Arcangeli A, Torri V, Bilancia D, Floriani I, Tonato M; Italian Oncology Group for Cancer Research. Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC. J Natl Cancer Inst. 2008 Mar 19;100(6):388-98. Epub 2008 Mar 11. link to original article PubMed
Kulig J, Kolodziejczyk P, Sierzega M, Bobrzynski L, Jedrys J, Popiela T, Dadan J, Drews M, Jeziorski A, Krawczyk M, Starzynska T, Wallner G. Adjuvant chemotherapy with etoposide, adriamycin and cisplatin compared with surgery alone in the treatment of gastric cancer: a phase III randomized, multicenter, clinical trial. Oncology. 2010;78(1):54-61. Epub 2010 Mar 6. link to original article PubMed
JCOG 9206-2: Miyashiro I, Furukawa H, Sasako M, Yamamoto S, Nashimoto A, Nakajima T, Kinoshita T, Kobayashi O, Arai K; Gastric Cancer Surgical Study Group in the Japan Clinical Oncology Group. Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2. Gastric Cancer. 2011 Aug;14(3):212-8. Epub 2011 Feb 19. link to original article PubMed

Pembrolizumab Monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Tabernero et. al, 2019 (KEYNOTE-062)	Randomized Phase III	Chemotherapy	May be superior

KEYNOTE-062 included patients with GEJ malignancy

*Improved OS was seen in patients with PD-L1 CPS score of 10 or more (HR: 0.62) but was not tested per analysis plan

Chemotherapy

Pembrolizumab (Keytruda) 200 mg IV daily on day 1

21-day cycles

References

Abstract: Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. DOI: 10.1200/JCO.2019.37.18_suppl.LBA4007 37, no. 18_suppl

Pembrolizumab + Cisplatin + 5-FU

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Regimen

Study	Evidence	Comparator	Efficacy
Tabernero et. al, 2019 (KEYNOTE-062)	Randomized Phase III	Cisplatin + 5-FU + Placebo	Inferior OS

KEYNOTE-062 included patients with GEJ malignancy

Chemotherapy

Pembrolizumab (Keytruda) 200 mg IV daily on day 1
Cisplatin 80 mg/m² on day 1
5-FU 800 mg/m² on days 1-5 OR capecitabine 1000 mg/m² PO BID on days 1-14

21-day cycles

References

Abstract: Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. DOI: 10.1200/JCO.2019.37.18_suppl.LBA4007 37, no. 18_suppl

S-1 monotherapy

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Variant #1, 21-day cycles

Study	Evidence	Comparator	Efficacy
Tsuburaya (SAMIT)	Phase III (C)	1. Paclitaxel, then S-1 2. Paclitaxel, then UFT	Seems not superior
Tsuburaya (SAMIT)	Phase III (C)	3. UFT	Superior DFS

Preceding treatment

R0 or R1 gastrectomy with at least D2 dissection, within 2 to 8 weeks

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) 80 mg/m² PO twice per day on days 1 to 14

21-day cycle for 16 cycles

Variant #2, 42-day cycles

Study	Evidence	Comparator	Efficacy
Sakuramoto et al. 2007 (ACTS-GC)	Phase III (E)	Observation	Superior OS
Yoshikawa et al. 2019 (OPAS-1)	Phase III (C)	S-1 x 6 mo	Inconclusive whether non-inferior

Preceding treatment

R0 gastrectomy with at least D2 dissection, within 6 weeks

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 28
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 28
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 28

42-day cycle for 8 cycles

References

ACTS-GC: Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. link to original article contains verified protocol PubMed
1. Update: Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. link to original article PubMed
SAMIT: Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, Tanabe K, Takahashi N, Imamura H, Tatsumoto N, Hara A, Nishikawa K, Fukushima R, Nozaki I, Kojima H, Miyashita Y, Oba K, Buyse M, Morita S, Sakamoto J. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):886-93. Epub 2014 Jun 18. link to original article contains verified protocol PubMed
OPAS-1: Yoshikawa T, Terashima M, Mizusawa J, Nunobe S, Nishida Y, Yamada T, Kaji M, Fukushima N, Hato S, Choda Y, Yabusaki H, Yoshida K, Ito S, Takeno A, Yasuda T, Kawachi Y, Katayama H, Fukuda H, Boku N, Sano T, Sasako M. Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104[OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol. 2019 Mar;4(3):208-216. Epub 2019 Jan 22. Erratum in: Lancet Gastroenterol Hepatol. 2019 Apr;4(4):e3. link to original article PubMed

Metastatic or locally advanced disease, first-line

Capecitabine monotherapy

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X: Xeloda (Capecitabine)

Variant #1, 2000 mg/m²/day

Study	Evidence	Comparator	Efficacy
Hwang et al. 2017	Phase III (C)	XELOX	Did not meet primary endpoint of OS

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycles

Variant #2, 2500 mg/m²/day

Study	Evidence
Hong et al. 2004	Phase II

Study only included patients with Karnofsky status of at least 70%

Chemotherapy

Capecitabine (Xeloda) 1250 mg/m² PO twice per day on days 1 to 14

21-day cycle for up to 6 cycles

References

Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. link to original article contains verified protocol PubMed
Hwang IG, Ji JH, Kang JH, Lee HR, Lee HY, Chi KC, Park SW, Lee SJ, Kim ST, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK. A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer. J Geriatr Oncol. 2017 May;8(3):170-175. Epub 2017 Jan 21. link to original article contains protocol PubMed

CapeOx

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CapeOX: Capecitabine & OXaliplatin

Regimen

Study	Evidence
Jatoi et al. 2006	Phase II

Chemotherapy

Capecitabine (Xeloda) 850 mg/m² PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1

21-day cycles

References

Jatoi A, Murphy BR, Foster NR, Nikcevich DA, Alberts SR, Knost JA, Fitch TR, Rowland KM Jr; North Central Cancer Treatment Group. Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. Ann Oncol. 2006 Jan;17(1):29-34. Epub 2005 Nov 22. link to original article contains protocol PubMed

Carboplatin & Paclitaxel

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Regimen

Study	Evidence
Philip et al. 1997	Phase II
Gadgeel et al. 2003	Phase II

Note: In contrast to the original reference, some guidelines list the dosage of carboplatin as AUC 6.

Philip et al. included patients with locally advanced metastatic or recurrent esophageal or gastric cancer

Gadgeel et al. study showed an ORR of 35%

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1, given second
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1, given first

21-day cycles

References

Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. contains protocol PubMed
Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003 Feb;26(1):37-41. link to original article contains protocol PubMed

Cisplatin & Docetaxel

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DC: Docetaxel, Cisplatin
TC: Taxotere (Docetaxel), Cisplatin

Variant #1, 75/75

Study	Evidence	Comparator	Efficacy
Roth et al. 2007	Randomized Phase II (E)	1. ECF	Not reported
Roth et al. 2007	Randomized Phase II (E)	2. TCF	Might have inferior ORR

Note: the protocol was amended to change the original dose of docetaxel from 85 mg/m² to 75 mg/m² based on high incidence of febrile neutropenia.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 4 hours once on day 1
Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1

Supportive medications

3 liters per day "hyperhydration"
Dexamethasone (Decadron) 8 mg PO given 12 hours & 6 hours before Docetaxel (Taxotere), then 8 mg PO twice per day for 4 days after Docetaxel (Taxotere)
5-HT3 antagonist for emesis prophylaxis
Growth factor support allowed, such as with Filgrastim (Neupogen)

21-day cycle for up to 8 cycles

Variant #2, 75/85

Study	Evidence	Comparator	Efficacy
Ajani et al. 2005 (V-325)	Randomized Phase II (C)	DCF	Seems to have inferior ORR

Patients: 100% adenocarcinoma histology (32% esophagogastric junction/fundus and 68% gastric antrum/body). 95% were metastatic. 1% with Karnofsky PS score of 70.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 1 to 3 hours once on day 1
Docetaxel (Taxotere) 85 mg/m² IV over 60 minutes once on day 1

Supportive medications

Dexamethasone (Decadron) 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (total dose per cycle: 48 mg)
Dexamethasone (Decadron) 20 mg IV before Cisplatin (Platinol) and 8 hours after Cisplatin (Platinol)
Ondansetron (Zofran) 8 mg IV before Cisplatin (Platinol), 4 hours after Cisplatin (Platinol), and 8 hours after Cisplatin (Platinol)
"Hydration was administered in a standard manner"

21-day cycles

References

V-325: Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. link to original article contains verified protocol PubMed
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. link to original article contains verified protocol PubMed

Cisplatin & Fluorouracil

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CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol (Cisplatin)

Variant #1, 80/4000 x 6

Study	Evidence	Comparator	Efficacy
Bang et al. 2010 (ToGA)	Phase III (C)	CF & Trastuzumab	Inferior OS

Patients in ToGA had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.

ToGA Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 1 to 3 hours once on day 1, given first
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 4000 mg/m²)

Supportive medications

Some protocols: "Hyperhydration" for Cisplatin (Platinol)

21-day cycle for up to 6 cycles

Variant #2, 80/4000 x 8

Study	Evidence	Comparator	Efficacy
Ajani et al. 2017 (DIGEST)	Phase III (C)	CS	Did not meet primary endpoint of OS

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 1 to 3 hours once on day 1, given first
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 4000 mg/m²)

Supportive medications

Some protocols: "Hyperhydration" for Cisplatin (Platinol)

21-day cycle for 8 cycles

Variant #3, 80/4000, indefinite

Study	Evidence	Comparator	Efficacy
Kang et al. 2009	Phase III (C)	CX	Non-inferior PFS

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 1 to 3 hours once on day 1, given first
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 4000 mg/m²)

Supportive medications

Some protocols: "Hyperhydration" for Cisplatin (Platinol)

21-day cycles

Variant #4, 100/4000

Study	Evidence	Comparator	Efficacy
Duffour et al. 2006 (FFCD 9404)	Phase III (C)	FLP	Inconclusive whether non-inferior ORR

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 60 minutes once on either day 1 or 2
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

28-day cycles

Variant #5, 100/4000, split-dose cisplatin

Study	Evidence	Comparator	Efficacy
Ohtsu et al. 2003 (JCOG 9205)	Phase III (E)	1. Fluorouracil	Did not meet primary endpoint of OS
Ohtsu et al. 2003 (JCOG 9205)	Phase III (E)	2. UFTM	Did not meet primary endpoint of OS

Study included patients with PFS of 2 (9.6%)

Chemotherapy

Cisplatin (Platinol) 20 mg/m² IV over 30 minutes once per day on days 1 to 5
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

28-day cycle for up to 6 cycles

Variant #6, 100/5000

Study	Evidence	Comparator	Efficacy
Van Cutsem et al. 2006 (TAX 325)	Phase III (C)	DCF	Seems to have inferior OS
Dank et al. 2008	Phase III (C)	IF	Might have inferior TTP
Ajani et al. 2010 (FLAGS)	Phase III (C)	CS	Did not meet primary endpoint of OS

Van Cutsem et al Patients: 100% adenocarcinoma histology (22% Esophagogastric junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS of 70.

Dank et al Patients: 100% adenocarcinoma histology (20% Esophagogastric junction, 80% gastric origin). 96% with metastatic disease. 1% with Karnofsky PS of 70.

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 1 to 3 hours once on day 1, given first
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 5000 mg/m² )

Supportive medications

As described in Dank et al. 2008:
"Hyperhydration" for 2 to 3 days with each infusion
Ondansetron (Zofran) IV for antiemetic prophylaxis
Dexamethasone (Decadron) IV for antiemetic prophylaxis, then PO for 2 to 3 days
Metoclopramide (Reglan) for antiemetic prophylaxis
Filgrastim (Neupogen) (dose not specified) SC once per day, starting on day 4, to be continued until ANC greater than 1000/uL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
Atropine (Atropen) prn cholinergic symptoms
Loperamide (Imodium) prn delayed diarrhea

28-day cycles

References

JCOG 9205: Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. link to original article contains verified protocol PubMed
FFCD 9404: Duffour J, Bouché O, Rougier P, Milan C, Bedenne L, Seitz JF, Buecher B, Legoux JL, Ducreux M, Vetter D, Raoul JL, François E, Ychou M. Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial). Anticancer Res. 2006 Sep-Oct;26(5B):3877-83. link to original article contains verified protocol PubMed
TAX 325: Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. link to original article contains verified protocol PubMed
Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. link to original article contains verified protocol PubMed
Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. link to original article contains verified protocol PubMed
FLAGS: Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. link to original article contains protocol PubMed
ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains verified protocol PubMed
AVAGAST: Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains verified protocol PubMed
DIGEST: Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. link to original article contains verified protocol PubMed

Cisplatin & S-1

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CS: Cisplatin & S-1
SP: S-1 & Platinol (Cisplatin)

Variant #1, q3wk ("SP3")

Study	Evidence	Comparator	Efficacy
Ryu et al. 2015 (SOS)	Phase III (E)	SP5	Seems to have superior PFS

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Tegafur, gimeracil, oteracil (S-1) 40 mg/m² PO twice per day on days 1 to 14

21-day cycles

Variant #2, q4wk

Study	Evidence	Comparator	Efficacy
Ajani et al. 2010 (FLAGS)	Phase III (E)	CF	Did not meet primary endpoint of OS
Ajani et al. 2017 (DIGEST)	Phase III (E)	CF	Did not meet primary endpoint of OS

Note: this is an experimental arm of a study where the primary endpoint was not met. Included because CS has been shown to be superior in comparison to other regimens (see above).

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 1 to 3 hours once on day 1
Tegafur, gimeracil, oteracil (S-1) 25 mg/m² PO twice per day on days 1 to 21

28-day cycles

Variant #3, q5wk ("SP5")

Study	Evidence	Comparator	Efficacy
Koizumi et al. 2008 (SPIRITS)	Phase III (E)	S-1	Seems to have superior OS
Yamada et al. 2014 (G-SOX)	Phase III (C)	SOX	Non-inferior PFS
Ryu et al. 2015 (SOS)	Phase III (C)	SP3	Seems to have inferior PFS
Fujitani et al. 2016 (REGATTA)	Non-randomized portion of RCT
Ishigami et al. 2018 (PHOENIX-GC)	Phase III (C)	IV/IP Paclitaxel & S-1	Might have inferior OS
Yamada et al. 2019 (JCOG1013)	Phase III (C)	Cisplatin, Docetaxel, S-1	Did not meet primary endpoint of OS

Note: in REGATTA, there was no difference in outcome amongst patients who did or did not undergo surgery.

Inclusion criteria for REGATTA included the presence of a single non-curable factor (ex: hepatic, peritoneal, and para-aortic mets), see link for further details

SPIRITS trial included patients with ECOG of 2 (3% of patients)

Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details

Preceding treatment

REGATTA: Non-laparoscopic gastrectomy with D1 lymphadenectomy versus no surgery; chemotherapy began within 8 weeks of surgery

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV once on day 8
Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 21
- BSA at least 1.25 m² and less than 1.5 m²: 50 mg PO twice per day on days 1 to 21
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 21

35-day cycles

References

SPIRITS: Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. link to original article contains verified protocol PubMed
FLAGS: Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. link to original article contains protocol PubMed
G-SOX: Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hamada C, Hyodo I. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015 Jan;26(1):141-8. Epub 2014 Oct 14. link to original article contains protocol PubMed
SOS: Ryu MH, Baba E, Lee KH, Park YI, Boku N, Hyodo I, Nam BH, Esaki T, Yoo C, Ryoo BY, Song EK, Cho SH, Kang WK, Yang SH, Zang DY, Shin DB, Park SR, Shinozaki K, Takano T, Kang YK; SOS study investigators. Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS). Ann Oncol. 2015 Oct;26(10):2097-101. Epub 2015 Jul 27. link to original article contains protocol PubMed
REGATTA: Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. Epub 2016 Jan 26. link to original article contains verified protocol PubMed
DIGEST: Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. link to original article contains verified protocol PubMed
PHOENIX-GC: Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. link to original article contains verified protocol PubMed
JCOG1013: Yamada Y, Boku N, Mizusawa J, Iwasa S, Kadowaki S, Nakayama N, Azuma M, Sakamoto T, Shitara K, Tamura T, Chin K, Hata H, Nakamori M, Hara H, Yasui H, Katayama H, Fukuda H, Yoshikawa T, Sasako M, Terashima M. Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 May 14. [Epub ahead of print] link to original article contains protocol PubMed

CLF

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CLF: Cisplatin, Leucovorin, Fluorouracil
FLP: Fluorouracil, Leucovorin, Platinol (Cisplatin)

Variant #1

Study	Evidence	Comparator	Efficacy
Al-Batran et al. 2008	Phase III (C)	FLO	Might have inferior PFS

Note: In contrast to the original reference, some guidelines list 5-FU as being given every 2 weeks rather than the schedule below.

Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric).

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Fluorouracil (5-FU) 2000 mg/m² IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 12,000 mg/m²)

Supportive medications

Up to 3 liters normal saline as hydration with Cisplatin (Platinol)
Antiemetic medications per "local protocols"

8-week cycles

Variant #2

Study	Evidence	Comparator	Efficacy
Bouché et al. 2004 (FFCD 9803)	Randomized Phase II (E)	1. LV5FU2 2. LV5FU2 & Irinotecan	Not powered to draw conclusions

Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more regular schedule was used.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 60 minutes once on either day 1 or 2
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 1200 mg/m² IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m²)

Supportive medications

1 liter hydration over 3 hours before and after Cisplatin (Platinol)
5-HT3 antagonist IV before Cisplatin (Platinol)
Methylprednisolone (Solumedrol) 120 mg IV 10 minutes before Cisplatin (Platinol)
Oral antiemetics and corticosteroids from days 2 to 5

14-day cycle for at least 4 cycles

References

FFCD 9803: Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. link to original article contains verified protocol PubMed
Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. link to original article contains verified protocol PubMed

CX

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CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Efficacy
Kang et al. 2009	Phase III (E)	CF	Non-inferior PFS
Ohtsu et al. 2011 (AVAGAST)	Phase III (C)	CX & Bevacizumab	Did not meet primary endpoint of OS
Lordick et al. 2013 (EXPAND)	Phase III (C)	CX & Cetuximab	Did not meet primary endpoint of PFS
Shen et al. 2014 (AVATAR)	Phase III (C)	CX & Bevacizumab	Did not meet primary endpoint of OS
Kim et al. 2014 (SMC 2008-12-019)	Phase III (C)	CX & Simvastatin	Did not meet primary endpoint of PFS
Lu et al. 2018 (PAC-C)	Phase III (C)	Capecitabine & Paclitaxel	Did not meet primary endpoint of PFS
Fuchs et al. 2019 (RAINFALL)	Phase III (C)	CX & Ramucirumab	Did not meet primary endpoint of PFS (*)

The following studies included patients with GE junction malignancy as well:

AVAGAST patients: 86% gastric and 14% GE junction. 5.4% of patients had an ECOG of 2.
EXPAND patients: 83% gastric, 5% GE junction and 16% unknown
Kim et al patients: 79% gastric, 16% GE junction and 5% unknown

Note: while the primary analysis of RAINFALL showed that this arm seemed to have inferior PFS, independent central review did not confirm this finding.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 2 hours once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
- EXPAND: 1000 mg/m² PO twice per day from the evening of day 1 to the morning of day 15 (28 doses per cycle)

Supportive medications

Some protocols: "Hyperhydration" for Cisplatin (Platinol)

21-day cycles, varied duration (see below)

Subsequent treatment

AVAGAST & AVATAR: after 6 cycles, capecitabine maintenance
Kim et al. 2014: after 8 cycles, capecitabine maintenance

References

Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. link to original article contains verified protocol PubMed content property of HemOnc.org
AVAGAST: Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains verified protocol PubMed
EXPAND: Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. link to original article contains verified protocol PubMed
AVATAR: Shen L, Li J, Xu J, Pan H, Dai G, Qin S, Wang L, Wang J, Yang Z, Shu Y, Xu R, Chen L, Liu Y, Yu S, Bu L, Piao Y. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015 Jan;18(1):168-76. Epub 2014 Feb 21. link to original article link to PMC article contains verified protocol PubMed
SMC 2008-12-019: Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. link to original article contains verified protocol PubMed
PAC-C: Lu Z, Zhang X, Liu W, Liu T, Hu B, Li W, Fan Q, Xu J, Xu N, Bai Y, Pan Y, Xu Q, Bai W, Xia L, Gao Y, Wang W, Shu Y, Shen L. A multicenter, randomized trial comparing efficacy and safety of paclitaxel/capecitabine and cisplatin/capecitabine in advanced gastric cancer. Gastric Cancer. 2018 Sep;21(5):782-791. Epub 2018 Feb 27. link to original article link to PMC article contains verified protocol PubMed
RAINFALL: Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA; RAINFALL Study Group. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):420-435. Epub 2019 Feb 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. link to original article contains protocol PubMed

CX & Trastuzumab

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CX & Trastuzumab: Cisplatin, Xeloda (Capecitabine), Trastuzumab

Variant #1, 80/1600

Study	Evidence	Comparator	Efficacy
Shah et al. 2017 (HELOISE)	Phase IIIb (C)	CX & Trastuzumab; high-dose	Did not meet primary endpoint of OS

Patients had overexpression of HER2 protein by immunohistochemistry AND gene amplification by in-situ hybridisation.

Patients: 79% gastric, 21% GE junction, and all patients had an ECOG of 2

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Capecitabine (Xeloda) 800 mg/m² PO twice per day on days 1 to 14
Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1 (compared to HD-Trastuzumab at 10 mg/kg IV)
- Subsequent cycles: 6 mg/kg IV once on day 1

21-day cycle for up to 6 cycles

Subsequent treatment

Trastuzumab maintenance

Variant #2, 80/2000

Study	Evidence	Comparator	Efficacy
Bang et al. 2010 (ToGA)	Phase III (E-RT)	CX	Superior OS
Tabernero et al. 2018 (JACOB)	Phase III (C)	CX, Pertuzumab, Trastuzumab	Might have inferior OS

ToGA patients had overexpression of HER2 protein by immunohistochemistry OR gene amplification by fluorescence in-situ hybridisation.

ToGA patients: 81% gastric, 19% GE junction. 10% of patients with ECOG of 2.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Subsequent cycles: 6 mg/kg IV once on day 1

21-day cycles

References

ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains verified protocol PubMed
HELOISE: Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.link to original article contains verified protocol PubMed
JACOB: Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. link to original article contains protocol PubMed

DCF

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DCF: Docetaxel, Cisplatin, Fluorouracil
TCF: Taxotere (Docetaxel), Cisplatin, Fluorouracil

Variant #1

Study	Evidence	Comparator	Efficacy
Ajani et al. 2005 (V-325)	Randomized Phase II (E)	DC	Seems to have superior ORR
Van Cutsem et al. 2006 (TAX 325)	Phase III (E-RT)	CF	Seems to have superior OS

Note: In contrast to the original references, some guidelines list each cycle as lasting 28 days.

Anjani et al. Patients: 100% adenocarcinoma histology (32% gastroesophageal junction/fundus and 68% gastric antrum/body). 95% were metastatic. 1% with Karnofsky PS score of 70.

Van Cutsem et al Patients: 100% adenocarcinoma histology (22% gastroesophageal junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS score of 70.

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1
Cisplatin (Platinol) 75 mg/m² IV over 1 to 3 hours once on day 1
Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m²)

Supportive medications

(varied depending on reference):
Dexamethasone (Decadron) 8 mg PO once the night before chemotherapy, then 8 mg PO once on day 1; 1 hour prior to chemotherapy, then 8 mg PO twice per day until day 2 (total dose per cycle: 48 mg)
Dexamethasone (Decadron) 20 mg IV before Cisplatin (Platinol) and 8 hours after Cisplatin (Platinol)
Ondansetron (Zofran) 8 mg IV before Cisplatin (Platinol), 4 hours after Cisplatin (Platinol), and 8 hours after Cisplatin (Platinol)
"Hydration [was] administered in a standard manner"

21-day cycles

Variant #2

Study	Evidence	Comparator	Efficacy
Roth et al. 2007	Randomized Phase II (E)	1. ECF	Not reported
Roth et al. 2007	Randomized Phase II (E)	2. TC	Might have superior ORR

Note: the protocol was amended to change the original dose of docetaxel from 85 mg/m² to 75 mg/m² based on high incidence of febrile neutropenia.

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1
Cisplatin (Platinol) 75 mg/m² IV over 4 hours once on day 1
Fluorouracil (5-FU) 300 mg/m²/day IV continuous infusion over 14 days, started on day 1 (total dose per cycle: 4200 mg/m²)

Supportive medications

3 liters per day "hyperhydration"
Dexamethasone (Decadron) 8 mg PO given 12 hours & 6 hours before Docetaxel (Taxotere), then 8 mg PO twice per day for 4 days after Docetaxel (Taxotere)
5-HT3 antagonist for emesis prophylaxis
Growth factor support allowed, such as with Filgrastim (Neupogen)

21-day cycle for up to 8 cycles

References

V-325: Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. link to original article contains verified protocol PubMed
TAX 325: Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. link to original article contains verified protocol PubMed
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. link to original article contains verified protocol PubMed

mDCF

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mDCF: modified Docetaxel, Cisplatin, Fluorouracil

Variant #1, 40/40/2800

Study	Evidence
Shah et al. 2010	Phase II

Note: In contrast to the primary reference, some guidelines list this regimen without bevacizumab. Please see below for the original mDCF regimen that included bevacizumab.

Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.

Chemotherapy

Docetaxel (Taxotere) 40 mg/m² IV over 60 minutes once on day 1
Cisplatin (Platinol) 40 mg/m² IV over 1 to 3 hours once on day 3
Folinic acid (Leucovorin) 400 mg/m² IV once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 1200 mg/m²/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m²)

Supportive medications

"Standard premedication and delayed emesis regimens"

14-day cycles

Variant #2, 60/60/3000

Study	Evidence	Comparator	Comparative Efficacy
Ozal et al. 2010	Phase II
Wang et al. 2015 (DOCET_L_02195)	Phase III (E)	CF	Seems to have superior OS

Chemotherapy

Docetaxel (Taxotere) 60 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) by one of the following:
- 600 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3000 mg/m²)
- 750 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 3000 mg/m²)

21-day cycles

References

Abstract: G. Ozal, M. Dogan, H. Akbulut, B. Yalcin, G. Utkan, Y. Urun, F. Icli. The safety and efficacy of modified-dose docetaxel, cisplatin, and 5-fluorouracil (mDCF) combination in the front-line treatment of advanced gastric cancer. 2010 Gastrointestinal Cancers Symposium abstract 113. link to abstract
Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. link to original article contains verified protocol link to PMC article PubMed
DOCET_L_02195: Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, Dai G, Xu J, Liu Y, Fan N, Shu Y, Ba Y, Ma D, Qin S, Zheng L, Chen W, Shen L. Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer. 2016 Jan;19(1):234-44. Epub 2015 Jan 21. link to original article link to PMC article contains verified protocol PubMed

mDCF & Bevacizumab

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mDCF & Bevacizumab: modified Docetaxel, Cisplatin, Fluorouracil & Bevacizumab

Regimen

Study	Evidence
Shah et al. 2010	Phase II

Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.

Chemotherapy

Docetaxel (Taxotere) 40 mg/m² IV over 60 minutes once on day 1
Cisplatin (Platinol) 40 mg/m² IV over 1 to 3 hours once on day 3
Folinic acid (Leucovorin) 400 mg/m² IV once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 1200 mg/m²/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m²)
Bevacizumab (Avastin) 10 mg/kg IV once on day 1

Supportive medications

"Standard premedication and delayed emesis regimens"

14-day cycles

References

Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. link to original article contains verified protocol link to PMC article PubMed

Docetaxel & S-1

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Regimen

Study	Evidence	Comparator	Efficacy
Koizumi et al. 2013 (START_gastric)	Phase III (E)	S-1	Seems to have superior OS

Chemotherapy

Docetaxel (Taxotere) 40 mg/m² IV once on day 1
Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 14
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 14
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 14

21-day cycles

References

START: Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. link to original article link to PMC article contains verified protocol PubMed

ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Findlay et al. 1994	Phase II
Webb et al. 1997	Phase III (E)	FAMTX	Superior OS
Ross et al. 2002	Phase III (C)	MCF	Seems to have non-inferior OS
Roth et al. 2007	Randomized Phase II (C)	1. TC 2. TCF	Not reported
Cunningham et al. 2008 (REAL-2)	Phase III (C)	1. ECX	Non-inferior OS
		2. EOF	Non-inferior OS
		3. EOX	Seems to have inferior OS

Findlay et al. Patients: all metastatic gastric cancer

Ross et al. Patients: adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma histology, all advanced esophagogastric cancer.

Roth et al. Patients: all metastatic gastric cancer

REAL-2 Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV bolus once on day 1
Cisplatin (Platinol) 60 mg/m² IV over 4 hours once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m²)

Supportive medications

(varied depending on reference):
3 liters per day "hyperhydration"
5-HT3 antagonist for emesis prophylaxis
Growth factor support allowed, such as with Filgrastim (Neupogen)
Ross et al. 2002 & Cunningham et al. 2008 used Warfarin (Coumadin) 1 mg PO once per day for catheter thrombosis prophylaxis

21-day cycle for up to 8 cycles

References

Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. link to original article contains verified protocol PubMed
Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997 Jan;15(1):261-7. link to original article contains verified protocol PubMed
1. Update: Waters JS, Norman A, Cunningham D, Scarffe JH, Webb A, Harper P, Joffe JK, Mackean M, Mansi J, Leahy M, Hill A, Oates J, Rao S, Nicolson M, Hickish T. Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer. 1999 Apr;80(1-2):269-72. link to original article link to PMC article PubMed
Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. link to original article contains verified protocol PubMed
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. link to original article contains verified protocol PubMed
REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains verified protocol PubMed

ECX

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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
ECC: Epirubicin, Cisplatin, Capecitabine

Variant #1, continuous capecitabine

Study	Evidence	Comparator	Efficacy
Catenacci et al. 2017 (RILOMET-1)	Randomized Phase II (C)	ECX & Rilotumumab	Superior OS

Patients had unresectable or metastatic MET-positive gastric or gastro-esophageal junction cancer.

Patients: ~80% gastric, 20% GE junction and 10% distal esophageal

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 625 mg/m² PO twice per day

21-day cycle for up to 10 cycles

Variant #2, intermittent capecitabine

Study	Evidence	Comparator	Efficacy
Konings et al. 2010	Randomized Phase II (C)	ECC & Pravastatin	Did not meet primary endpoint of PFS6

Patients: 6.6% of patients had an ECOG of 2

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV bolus once on day 1, given first
Cisplatin (Platinol) 60 mg/m² IV over 3 hours once on day 1, given second
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for up to 6 cycles

References

Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010 Dec;46(18):3200-4. Epub 2010 Aug 18. link to original article contains verified protocol PubMed
RILOMET-1: Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. Epub 2017 Sep 25. link to original article contains verified protocol PubMed

Fluorouracil monotherapy

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Variant #1, CI

Study	Evidence	Comparator	Efficacy
Ohtsu et al. 2003 (JCOG 9205)	Phase III (C)	1. FP	Did not meet primary endpoint of OS
Ohtsu et al. 2003 (JCOG 9205)	Phase III (C)	2. UFTM	Did not meet primary endpoint of OS
Boku et al. 2009 (JCOG 9912)	Phase III (C)	1. Cisplatin & Irinotecan	Might have inferior OS
Boku et al. 2009 (JCOG 9912)	Phase III (C)	2. S-1	Non-inferior OS
Shirao et al. 2013 (JCOG 0106)	Phase III (C)	MF	Did not meet primary endpoint of OS50%

JCOG 9205 included patients with PFS of 2 (9.6%)

Chemotherapy

Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

28-day cycles

Variant #2, intermittent, BSA-based

Study	Evidence	Comparator	Efficacy
Cullinan et al. 1985	Phase III (E)	1. FA 2. FAM	Did not meet primary endpoint of OS

Note: this is an experimental arm that did not meet its primary endpoint; included here because it represents a de-escalation strategy.

Chemotherapy

Fluorouracil (5-FU) 500 mg/m² IV once per day on days 1 to 5

28-day cycle for 2 cycles, then 35-day cycles

Variant #3, intermittent, weight-based

Study	Evidence	Comparator	Efficacy
Kolarić et al. 1986	Phase III (C)	Epirubicin & Fluorouracil	Seems to have inferior DOR

Chemotherapy

Fluorouracil (5-FU) 12 mg/kg IV once per day on days 1 to 5

21- to 28-day cycles

Variant #4, PVI

Study	Evidence	Comparator	Efficacy
Tebbutt et al. 2002	Phase III (C)	5-FU & Mitomycin	Did not meet primary endpoint of ORR

Chemotherapy

Fluorouracil (5-FU) 300 mg/m²/day IV continuous infusion

Up to 24-week course

References

Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, Pfeifle DM, Barlow JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma: fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985 Apr 12;253(14):2061-7. link to original article PubMed
Kolarić K, Potrebica V, Stanovnik M. Controlled phase III clinical study of 4-epi-doxorubicin + 5-fluorouracil versus 5-fluorouracil alone in metastatic gastric and rectosigmoid cancer. Oncology. 1986;43(2):73-7. link to original article contains protocol PubMed
Tebbutt NC, Norman A, Cunningham D, Iveson T, Seymour M, Hickish T, Harper P, Maisey N, Mochlinski K, Prior Y, Hill M. A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer. Ann Oncol. 2002 Oct;13(10):1568-75. link to original article contains verified protocol PubMed
JCOG 9205: Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. link to original article contains verified protocol PubMed
JCOG 9912: Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. link to original article contains protocol PubMed
JCOG 0106: Shirao K, Boku N, Yamada Y, Yamaguchi K, Doi T, Goto M, Nasu J, Denda T, Hamamoto Y, Takashima A, Fukuda H, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Randomized Phase III study of 5-fluorouracil continuous infusion vs sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106). Jpn J Clin Oncol. 2013 Oct;43(10):972-80. Epub 2013 Sep 7. link to original article contains verified protocol PubMed

Fluorouracil, Folinic acid, Mitomycin

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Regimen

Study	Evidence
Hofheinz et al. 2002	Phase II, <20 pts in this subgroup

Chemotherapy

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours once per day on days 1, 8, 15, 22, 29, 36
Folinic acid (Leucovorin) 500 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
Mitomycin (Mutamycin) 10 mg/m² IV once per day on days 1 & 22

56-day cycle for 2 cycles

References

Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. link to original article contains protocol PubMed

Irinotecan monotherapy

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Regimen

Study	Evidence
Enzinger et al. 2005	Phase II

Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m² IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."

Study included patients with GE junction and distal esophageal malignancy as well (~59% gastric, 9% GEJ and 33% distal esophagus)

Regimen showed a 14% response rate and 53% disease control rate.

Chemotherapy

Irinotecan (Camptosar) 125 mg/m² IV over 90 minutes once per day on days 1, 8, 15, 22

42-day cycles

References

Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. link to original article PubMed

OLF

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OLF: Oxaliplatin, Leucovorin, Fluorouracil
FLO: Fluorouracil, Leucovorin, Oxaliplatin

Regimen

Study	Evidence	Comparator	Efficacy
Al-Batran et al. 2008	Phase III (E)	FLP	Might have superior PFS

Patients: 100% adenocarcinoma histology (20% esophagogastric junction, 80% gastric).

Chemotherapy

Oxaliplatin (Eloxatin) 85 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours, started on days 1, 15, 29, 43 (total dose per cycle: 10,400 mg/m²)

Supportive medications

Antiemetic medications per "local protocols"

8-week cycles

References

Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. link to original article contains verified protocol PubMed

Paclitaxel & S-1

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Regimen

Study	Evidence	Comparator	Efficacy
Ishigami et al. 2018 (PHOENIX-GC)	Phase III (C)	Cisplatin & S-1	Might have superior OS

Note: Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details

Chemotherapy

Paclitaxel (Taxol) 50 mg/m² IV once per day on days 1 and 8
Tegafur, gimeracil, oteracil (S-1) as follows:
- 40 to 60 mg twice per day, depending on body surface area, as follows:
  - if less than 1.25 m²: 40 mg PO twice per day on days 1 to 14
  - if 1.25 to less than 1.5 m²: 50 mg PO twice per day on days 1 to 14
  - if more than 1.5 m²: 60 mg PO twice per day on days 1 to 14
Paclitaxel (Taxol) 20 mg/m² IP once per day over 1 hour on days 1 and 8

Supportive medications

500 mL of normal saline was given prior to intraperitoneal Paclitaxel (Taxol)

35-day cycles

References

PHOENIX-GC: Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. link to original article contains verified protocol PubMed

S-1 monotherapy

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Variant #1, BSA-based

Study	Evidence	Comparator	Efficacy
Boku et al. 2009 (JCOG 9912)	Phase III (E)	1. Cisplatin & Irinotecan	Not reported
Boku et al. 2009 (JCOG 9912)	Phase III (E)	2. 5-FU	Non-inferior OS

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) 40 mg/m² PO twice per day on days 1 to 28

42-day cycles

Variant #2, weight-based

Study	Evidence	Comparator	Efficacy
Koizumi et al. 2008 (SPIRITS)	Phase III (C)	Cisplatin & S-1	Seems to have inferior OS
Narahara et al. 2011 (TOP-002)	Phase III (C)	IRIS	Did not meet primary endpoint of OS
Koizumi et al. 2013 (START_gastric)	Phase III (C)	Docetaxel & S-1	Seems to have inferior OS
Yoshino et al. 2016 (JFMC36-0701)	Phase III (C)	Lentinan & S-1	Did not meet primary endpoint of OS

Note: there is another trial named START in NSCLC.

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 28
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 28
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 28

42-day cycles

References

SPIRITS: Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. link to original article contains verified protocol PubMed
JCOG 9912: Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. link to original article contains protocol PubMed
TOP-002: Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, Imamoto H, Esaki T, Furukawa H, Hamada C, Sakata Y. Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002). Gastric Cancer. 2011 Mar;14(1):72-80. Epub 2011 Feb 23. link to original article link to PMC article contains verified protocol PubMed
START: Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. link to original article link to PMC article contains verified protocol PubMed
JFMC36-0701: Yoshino S, Nishikawa K, Morita S, Takahashi T, Sakata K, Nagao J, Nemoto H, Murakami N, Matsuda T, Hasegawa H, Shimizu R, Yoshikawa T, Osanai H, Imano M, Naitoh H, Tanaka A, Tajiri T, Gochi A, Suzuki M, Sakamoto J, Saji S, Oka M. Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur J Cancer. 2016 Sep;65:164-71. Epub 2016 Aug 5. link to original article PubMed

UFTM

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UFTM: UFT (Tegafur and uracil) & Mitomycin

Regimen

Study	Evidence	Comparator	Efficacy
Ohtsu et al. 2003 (JCOG 9205)	Phase III (E)	1. Fluorouracil	Did not meet primary endpoint of OS
Ohtsu et al. 2003 (JCOG 9205)	Phase III (E)	2. FP	Did not meet primary endpoint of OS

Study included patients with PFS of 2 (9.6%)

Chemotherapy

Tegafur and uracil (UFT) 187.5 mg/m² PO twice per day
Mitomycin (Mutamycin) 5 mg/m² IV once per day on days 1, 8, 15, 22
- "Mitomycin was interrupted for 1 month after patients received a total dose of 60 mg."

28-day cycles

References

JCOG 9205: Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. link to original article contains verified protocol PubMed

Maintenance after first-line therapy

Capecitabine monotherapy

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Regimen

Study	Evidence
Ohtsu et al. 2011 (AVAGAST)	Non-randomized portion of RCT
Kim et al. 2014	Non-randomized portion of RCT

Ohtsu et al patients: 86% gastric and 14% GEJ. 5.4% of patients had an ECOG of 2.

Kim et al patients: 79% gastric, 5% GEJ, and 16% unknown. 2% of patients had an ECOG of 2.

Preceding treatment

AVAGAST: CX x 6
Kim et al. 2014: CX x 8

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycles

References

Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains verified protocol PubMed
Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. link to original article contains verified protocol PubMed

Metastatic or locally advanced disease, subsequent lines of therapy

Best supportive care

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Regimen

Study	Evidence	Comparator	Efficacy
Thuss-Patience et al. 2011	Phase III (C)	Irinotecan	Seems to have inferior OS
Kang et al. 2012	Phase III (C)	1. Docetaxel 2. Irinotecan	Inferior OS
Ford et al. 2014 (COUGAR-02)	Phase III (C)	Docetaxel	Inferior OS
Ohtsu et al. 2013 (GRANITE-1)	Phase III (C)	Everolimus	Seems not superior

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

Thuss-Patience et al. patients: ~58% gastric, 43% GEJ. 21% of patients had an ECOG of 2.

GRANITE-1 study patients: 29% had GEJ involvement. 7.9% of patients had an ECOG of 2.

References

Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains verified protocol PubMed
Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed
COUGAR-02: Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. link to original article contains protocol PubMed
GRANITE-1: Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, Sahmoud T, Shen L, Yeh KH, Chin K, Muro K, Kim YH, Ferry D, Tebbutt NC, Al-Batran SE, Smith H, Costantini C, Rizvi S, Lebwohl D, Van Cutsem E. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013 Nov 1;31(31):3935-43. Epub 2013 Sep 16. link to original article PubMed

Apatinib monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Kang et al. 2019 (ANGEL)	Randomized Phase III	Placebo	Superior PFS

ANGEL included patients with GEJ malignancy

Chemotherapy

Apatinib (Rivoceranib) 700 mg daily on days 1-28

28-day cycles

References

Abstract: Kang Y, Kang WK, Di Bartolomeo M, Chau I, Yoon HH, Cascinu S, Ryu M, Kim JG, Lee K, Oh SC, Takashima A, Kryzhanivska A, Chao Y, Vladimirov V, Evesque L, Schenker M, McGinn A, Sankar N, Wyrwicz L, Boku N. Randomized Phase 3 ANGEL study of rivoceranib (apatinib) + best supportive care (BSC) vs placebo + BSC in patients with advanced/metastatic gastric cancer. 2019 European Society of Medical Oncology annual meeting. Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Docetaxel monotherapy

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Variant #1, 60 mg/m²

Study	Evidence	Comparator	Efficacy
Kang et al. 2012	Phase III (E)	Best supportive care	Superior OS

Chemotherapy

Docetaxel (Taxotere) 60 mg/m² IV once on day 1

21-day cycles

Variant #2, 75 mg/m² x 6

Study	Evidence	Comparator	Efficacy
Ford et al. 2014 (COUGAR-02)	Phase III (E)	Best supportive care	Superior OS

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycle for up to 6 cycles

Variant #3, 75 mg/m², indefinite

Study	Evidence	Comparator	Efficacy
Thuss-Patience et al. 2017 (GATSBY)	Phase III (C)	T-DM1	Seems not superior

Patients in GATSBY had HER2-positive disease. Study patients could only have been treated by one other regimen and could not have been exposed to anthracyclines

Patients: 68% gastric, 32% GEJ

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycles

References

Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article contains protocol PubMed
COUGAR-02: Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. link to original article contains protocol PubMed
GATSBY: Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains protocol PubMed

Fluorouracil, Folinic acid, Mitomycin

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Regimen

Study	Evidence
Hofheinz et al. 2002	Phase II, <20 pts in this subgroup

Chemotherapy

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours once per day on days 1, 8, 15, 22, 29, 36
Folinic acid (Leucovorin) 500 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
Mitomycin (Mutamycin) 10 mg/m² IV once per day on days 1 & 22

56-day cycle for 2 cycles

References

Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. link to original article contains protocol PubMed

Irinotecan monotherapy

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Variant #1, 125 mg/m², 4 weeks out of 6

Study	Evidence
Enzinger et al. 2005	Phase II

Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m² IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."

Study included patients with GE junction and distal esophageal malignancy as well (~59% gastric, 9% GE junction and 33% distal esophagus)

Regimen showed a 14% response rate and 53% disease control rate.

Chemotherapy

Irinotecan (Camptosar) 125 mg/m² IV over 90 minutes once per day on days 1, 8, 15, 22

42-day cycles

Variant #2, 150 mg/m² q2wk

Study	Evidence	Comparator	Efficacy
Kang et al. 2012	Phase III (E)	Best supportive care	Superior OS
Hironaka et al. 2013 (WJOG 4007)	Phase III (E)	Paclitaxel	Seems not superior
Higuchi et al. 2014 (BIRIP)	Phase III (C)	Cisplatin & Irinotecan	Seems to have inferior PFS
Nishikawa et al. 2015 (TRICS)	Phase III (C)	Cisplatin & Irinotecan	Seems not superior
Tanabe et al. 2015 (JACCRO GC-05)	Phase III (C)	Irinotecan & S-1	Seems not superior
Bang et al. 2018 (JAVELIN Gastric 300)	Phase III (C)	Avelumab	Seems not superior

Hironaka et al patients: 3.7% patients with an ECOG PS of 2

Chemotherapy

Irinotecan (Camptosar) 150 mg/m² IV once on day 1

14-day cycles

Variant #3, 300 mg/m² q3wk

Study	Evidence	Comparator
Roy et al. 2013 (PEP0206)	Randomized Phase II (C)	1. Docetaxel 2. Irinotecan liposome

Study included patients with GE junction malignancy (77% gastric, 23% GE junction) and included patients with ECOG of 2

Chemotherapy

Irinotecan (Camptosar) 300 mg/m² IV over 90 minutes once on day 1

21-day cycles

Variant #4, 350 mg/m² q3wk

Study	Evidence	Comparator	Efficacy
Thuss-Patience et al. 2011	Phase III (E)	Best supportive care	Seems to have superior OS

Thuss-Patience et al. included patients with GE junction malignancy (~58% gastric, 43% GE junction) and included patients with ECOG of 2

Chemotherapy

Irinotecan (Camptosar) as follows:
- Cycle 1: 250 mg/m² (maximum dose of 500 mg) IV over 30 minutes once on day 1
- Cycles 2 to 10 (depending on toxicity): 350 mg/m² IV over 30 minutes once on day 1

Supportive medications

Atropine (Atropen) 0.25 mg SC once on day 1, given prior to Irinotecan (Camptosar)
5-HT3 antagonist
Dexamethasone (Decadron)

21-day cycle for up to 10 cycles

References

Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. link to original article PubMed
Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains verified protocol PubMed
Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed
PEP0206: Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. link to original article PubMed
WJOG 4007: Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. link to original artile contains protocol PubMed
BIRIP: Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, Takeda Y, Moriwaki T, Amagai K, Sekikawa T, Sakuyama T, Kanda T, Sasaki T, Azuma M, Takahashi F, Takeuchi M, Koizumi W; Tokyo Cooperative Oncology Group, Tokyo, Japan. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014 May;50(8):1437-45. Epub 2014 Feb 20. link to original article contains protocol PubMed
TRICS: Nishikawa K, Fujitani K, Inagaki H, Akamaru Y, Tokunaga S, Takagi M, Tamura S, Sugimoto N, Shigematsu T, Yoshikawa T, Ishiguro T, Nakamura M, Morita S, Miyashita Y, Tsuburaya A, Sakamoto J, Tsujinaka T. Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial. Eur J Cancer. 2015 May;51(7):808-16. Epub 2015 Mar 18. link to original article contains protocol PubMed
JACCRO GC-05: Tanabe K, Fujii M, Nishikawa K, Kunisaki C, Tsuji A, Matsuhashi N, Takagane A, Ohno T, Kawase T, Kochi M, Yoshida K, Kakeji Y, Ichikawa W, Chin K, Terashima M, Takeuchi M, Nakajima T; JACCRO GC-05 study group. Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05). Ann Oncol. 2015 Sep;26(9):1916-22. Epub 2015 Jun 24. link to original article PubMed
JAVELIN Gastric 300: Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. link to original article link to PMC article contains protocol PubMed

Irinotecan liposomal monotherapy

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Regimen

Study	Evidence	Comparator
Roy et al. 2013 (PEP0206)	Randomized Phase II (E)	1. Docetaxel 2. Irinotecan

Chemotherapy

Irinotecan liposome (Onivyde) 120 mg/m² IV over 90 minutes once on day 1

21-day cycles

References

PEP0206: Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. link to original article contains verified protocol PubMed

Nivolumab monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Kang et al. 2017 (ATTRACTION-2)	Phase III (E)	Placebo	Superior OS
Janjigian et al. 2018 (CheckMate-032)	Phase II

ATTRACTION-2 included patients with GE junction malignancy (82.6% gastric, 8.5% GE junction) and 12.3% of patients had a PD-L1 CPS score of at least 1

Immunotherapy

Nivolumab (Opdivo) 3 mg/kg IV once on day 1

14-day cycles

References

ATTRACTION-2: Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. link to original article contains verified protocol PubMed
1. Subgroup analysis: Kato K, Satoh T, Muro K, Yoshikawa T, Tamura T, Hamamoto Y, Chin K, Minashi K, Tsuda M, Yamaguchi K, Machida N, Esaki T, Goto M, Komatsu Y, Nakajima TE, Sugimoto N, Yoshida K, Oki E, Nishina T, Tsuji A, Fujii H, Kunieda K, Saitoh S, Omuro Y, Azuma M, Iwamoto Y, Taku K, Fushida S, Chen LT, Kang YK, Boku N. A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2). Gastric Cancer. 2019 Mar;22(2):344-354. Epub 2018 Dec 1. link to original article link to original article PubMed
CheckMate-032: Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, Ott PA, Peltola K, Jaeger D, Evans J, de Braud F, Chau I, Harbison CT, Dorange C, Tschaika M, Le DT. CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. J Clin Oncol. 2018 Oct 1;36(28):2836-2844. Epub 2018 Aug 15. link to original article link to PMC article PubMed

Paclitaxel monotherapy

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Variant #1, 70 mg/m², 3 out of 4 weeks

Study	Evidence	Comparator	Efficacy
Lee et al. 2018 (KCSG ST10-01)	Phase III (C)	Irinotecan	Inconclusive whether non-inferior

Chemotherapy

Paclitaxel (Taxol) 70 mg/m² IV once per day on days 1, 8, 15

28-day cycles

Variant #2, 80 mg/m² weekly

Study	Evidence	Comparator	Efficacy
Kodera et al. 2007 (CCOG0302)	Phase II
Thuss-Patience et al. 2017 (GATSBY)	Phase III (C)	T-DM1	Seems not superior

Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation

Study included patients with GE junction malignancy (68% gastric, 32% GE junction)

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

21-day cycles

Variant #3, 80 mg/m², 3 out of 4 weeks

Study	Evidence	Comparator	Efficacy
Hironaka et al. 2006	Non-randomized
Hironaka et al. 2013 (WJOG 4007)	Phase III (E)	Irinotecan	Seems not superior
Satoh et al. 2014 (TyTAN)	Phase III (C)	Lapatinib & Paclitaxel	Seems not superior
Wilke et al. 2014 (RAINBOW)	Phase III (C)	Paclitaxel & Ramucirumab	Seems to have inferior OS
Shitara et al. 2017 (ABSOLUTE)	Phase III (C)	1. nab-Paclitaxel weekly	Non-inferior OS
Shitara et al. 2017 (ABSOLUTE)	Phase III (C)	2. nab-Paclitaxel q3wk	Might have superior OS
Bang et al. 2017 (GOLD)	Phase III (C)	Olaparib & Paclitaxel	Might have inferior OS
Shitara et al. 2018 (KEYNOTE-061)	Phase III (C)	Pembrolizumab	Might have inferior OS
Bang et al. 2018 (JAVELIN Gastric 300)	Phase III (C)	Avelumab	Seems not superior

Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline." Patients in TyTAN had HER2-positive disease.

RAINBOW included patients with GE junction malignancy (79% gastric, 21% GE junction)

Satoh et al. patients: 98.5% gastric. 1.5 other

Hironaka et al patients: 3.7% patients with a PFS of 2

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

Variant #4, 175 mg/m² q3wk

Study	Evidence	Comparator	Efficacy
Kang et al. 2018 (DREAM)	Phase III (C)	DHP107	Non-inferior PFS

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycles

References

Hironaka S, Zenda S, Boku N, Fukutomi A, Yoshino T, Onozawa Y. Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2006;9(1):14-8. link to original article contains verified protocol PubMed
CCOG0302: Kodera Y, Ito S, Mochizuki Y, Fujitake S, Koshikawa K, Kanyama Y, Matsui T, Kojima H, Takase T, Ohashi N, Fujiwara M, Sakamoto J, Akimasa N; Chubu Clinical Cancer Group. A phase II study of weekly paclitaxel as second-line chemotherapy for advanced gastric cancer (CCOG0302 study). Anticancer Res. 2007 Jul-Aug;27(4C):2667-71. link to original article contains protocol PubMed
WJOG 4007: Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. link to original artile contains protocol PubMed
TyTAN: Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. link to original article contains verified protocol PubMed
RAINBOW: Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains verified protocol PubMed
ABSOLUTE: Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. link to original article contains protocol PubMed
GATSBY: Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains protocol PubMed
GOLD: Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. Epub 2017 Nov 2. link to original article PubMed
DREAM: Kang YK, Ryu MH, Park SH, Kim JG, Kim JW, Cho SH, Park YI, Park SR, Rha SY, Kang MJ, Cho JY, Kang SY, Roh SY, Ryoo BY, Nam BH, Jo YW, Yoon KE, Oh SC. Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus IV paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Ann Oncol. 2018 May 1;29(5):1220-1226. link to original article contains protocol PubMed
KEYNOTE-061: Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. link to original article contains verified protocol PubMed
KCSG ST10-01: Lee KW, Maeng CH, Kim TY, Zang DY, Kim YH, Hwang IG, Oh SC, Chung JS, Song HS, Kim JW, Jeong SJ, Cho JY. A phase III study to compare the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer who failed in first-line therapy (KCSG ST10-01). Oncologist. 2019 Jan;24(1):18-e24. Epub 2018 Aug 20. link to original article contains protocol link to PMC article PubMed
JAVELIN Gastric 300: Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. link to original article link to PMC article contains protocol PubMed

nab-Paclitaxel monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Shitara et al. 2017 (ABSOLUTE)	Phase III (E)	1. Weekly Paclitaxel	Non-inferior OS
Shitara et al. 2017 (ABSOLUTE)	Phase III (E)	2. nab-Paclitaxel q3wk	Not reported

Chemotherapy

Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m² IV once per day on days 1, 8, 15

28-day cycles

References

ABSOLUTE: Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. link to original article contains protocol PubMed

Paclitaxel & Ramucirumab

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Regimen

FDA-recommended dose

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy
Wilke et al. 2014 (RAINBOW)	Phase III (E-RT)	28% (95% CI 23-33%)	Paclitaxel	16% (95% CI 13-20%)	Seems to have superior OS

Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."

RAINBOW included patients with GE junction malignancy (79% gastric, 21% GE junction).

Chemotherapy

Ramucirumab (Cyramza) 8 mg/kg IV over 60 minutes once per day on days 1 & 15, given first
Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15, given second

28-day cycles

References

RAINBOW: Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains verified protocol PubMed

Pembrolizumab monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Fuchs et al. 2018 (KEYNOTE-059)	Phase II (RT)		ORR: 12% (95% CI 8-16)
Shitara et al. 2018 (KEYNOTE-061)	Phase III (E)	Paclitaxel	Might have superior OS

Both studies included patients with GE junction malignancy:

KEYNOTE-059: 48.3% gastric, 51.4% GE junction and 57.1% of patients had a PD-L1 CPS score of at least 1

KEYNOTE-061: 68.8% gastric, 31.2% GE junction and 66% of all patients receiving pembrolizumab had a PD-L1 CPS score of at least 1

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycle for up to 35 cycles (2 years)

References

KEYNOTE-059: Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018 May 10;4(5):e180013. Epub 2018 May 10. link to original article link to PMC article contains verified protocol PubMed
KEYNOTE-061: Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. link to original article contains verified protocol PubMed

Placebo

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Regimen

Study	Evidence	Comparator	Efficacy
Fuchs et al. 2013 (REGARD)	Phase III (C)	Ramucirumab	Seems to have inferior OS
Pavlakis et al. 2016 (INTEGRATE)	Randomized Phase II (C)	Regorafenib	Inferior PFS
Kang et al. 2017 (ATTRACTION-2)	Randomized Phase II (C)	Nivolumab	Inferior OS
Shitara et al. 2018 (TAGS)	Phase III (C)	Trifluridine/tipiracil	Inferior OS

All studies included patients with GE junction malignancy:

REGARD: 75% gastric, 25% GE junction
INTEGRATE: 62% stomach or other, 38% GE junction
ATTRACTION-2: 82.6% gastric, 8.5% GE junction

Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."

No active antineoplastic treatment.

References

REGARD: Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3.link to original article contains verified protocol PubMed
INTEGRATE: Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. link to original article contains verified protocol link to PMC article PubMed
ATTRACTION-2: Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. link to original article contains verified protocol PubMed
TAGS: Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. link to original article contains protocol PubMed

Ramucirumab monotherapy

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Regimen

FDA-recommended dose

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy
Fuchs et al. 2013 (REGARD)	Phase III (E-RT)	3%	Placebo	3%	Seems to have superior OS

Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."

Study includes patients with GE junction malignancy (75% gastric, 25% GE junction).

Chemotherapy

Ramucirumab (Cyramza) 8 mg/kg IV over 60 minutes once on day 1

14-day cycles

References

REGARD: Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. link to original article contains verified protocol PubMed

Regorafenib monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Pavlakis et al. 2016 (INTEGRATE)	Randomized Phase II (E)	Placebo	Superior PFS

INTEGRATE included patients with GEJ malignancy: 62% stomach or other, 38% GEJ

Chemotherapy

Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21

28-day cycles

References

INTEGRATE: Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. link to original article contains verified protocol link to PMC article PubMed

Trifluridine and tipiracil monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Shitara et al. 2018 (TAGS)	Phase III (E-RT)	Placebo	Superior OS

Chemotherapy

Trifluridine and tipiracil (Lonsurf) 35 mg/m² PO twice per day on days 1 to 5, 8 to 12

28-day cycles

References

TAGS: Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. link to original article contains protocol PubMed

@@ Line 19: / Line 19: @@
 =Guidelines=
 ==CAP/ASCP/ASCO==
 *'''2017:''' Bartley et al. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.4836 HER2 testing and clinical decision making in gastroesophageal adenocarcinoma] [https://www.ncbi.nlm.nih.gov/pubmed/28129524 PubMed]
 ==[http://www.esmo.org/ ESMO]==
 *'''2016:''' Smyth et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Gastric-Cancer Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/27664260 PubMed]
 ==ESMO/ESSO/ESTRO==
 *'''2013:''' Waddell et al. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdt344 Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/24078663 PubMed]
 ==[https://www.nccn.org/ NCCN]==
 *[https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf NCCN Guidelines - Gastric Cancer]
@@ Line 54: / Line 58: @@
 ''Study included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
@@ Line 59: / Line 64: @@
 '''28-day cycle for 2 to 3 cycles'''
 ====Subsequent treatment====
 *[[Surgery#Gastrectomy|Surgical resection]], then [[#Cisplatin_.26_Fluorouracil_2|adjuvant cisplatin & 5-FU]]
 ===References===
-# '''ACCORD 07:''' Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. [http://jco.ascopubs.org/content/29/13/1715.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21444866 PubMed]
+#'''ACCORD 07:''' Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. [http://jco.ascopubs.org/content/29/13/1715.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21444866 PubMed]
 ==ECF {{#subobject:f0281c|Regimen=1}}==
@@ Line 94: / Line 101: @@
 ''MAGIC included patients with lower esophageal malignancy as well (74% gastric, 14.8% lower esophagus, and 11.2% GE junction).''
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
@@ Line 99: / Line 107: @@
 ====Supportive medications====
 *MAGIC, suggested as thrombosis prophylaxis:
 **[[Warfarin (Coumadin)]] 1 mg PO once per day
@@ Line 104: / Line 113: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *MAGIC: [[Surgery#Gastrectomy|Surgical resection]] is performed 3 to 6 weeks after the completion of cycle 3, followed in 6 to 12 weeks by [[#ECF_2|adjuvant ECF]]
 *CRITICS: [[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection, then adjuvant [[#ECF_2|ECF]] versus capecitabine, cisplatin, RT
 ===References===
-# '''MAGIC:''' Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
-# '''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
+#'''MAGIC:''' Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
 ==ECX {{#subobject:c8ab0e|Regimen=1}}==
@@ Line 129: / Line 140: @@
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
@@ Line 135: / Line 147: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection, then adjuvant [[#ECX_2|ECX]] versus capecitabine, cisplatin, RT
 ===References===
-# '''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
 ==EOF {{#subobject:139705|Regimen=1}}==
@@ Line 158: / Line 172: @@
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
@@ Line 164: / Line 179: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection, then adjuvant [[#EOF_2|EOF]] versus capecitabine, cisplatin, RT
 ===References===
-# '''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
 ==EOX {{#subobject:86ee8e|Regimen=1}}==
@@ Line 187: / Line 204: @@
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
@@ Line 193: / Line 211: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection, then adjuvant [[#EOX_2|EOX]] versus capecitabine, cisplatin, RT
 ===References===
-# '''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
 ==FLOT {{#subobject:aa7f4f|Regimen=1}}==
@@ Line 214: / Line 234: @@
 | style="background-color:#1a9851" |Phase II/III (E)
 |ECF/ECX [[Complex_multipart_regimens#FLOT4-AIO|See link]]
-|style="background-color:#91cf60"|Seems to have superior OS [[Complex_multipart_regimens#FLOT4-AIO|See link]]
+| style="background-color:#91cf60" |Seems to have superior OS [[Complex_multipart_regimens#FLOT4-AIO|See link]]
 |-
 |}
@@ Line 220: / Line 240: @@
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 1
 *[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1
@@ Line 227: / Line 248: @@
 '''14-day cycle for 4 cycles'''
 ====Subsequent treatment====
 *[[Surgery#Gastrectomy|Surgery]], then [[#FLOT_2|adjuvant FLOT]]
 ===References===
-# '''FLOT4-AIO:''' Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30531-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27776843 PubMed]
-## '''Update:''' Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 Apr 10. [Epub ahead of print] [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32557-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30982686 PubMed]
+#'''FLOT4-AIO:''' Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30531-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27776843 PubMed]
+##'''Update:''' Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 Apr 10. [Epub ahead of print] [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32557-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30982686 PubMed]
 ==No neoadjuvant therapy==
@@ Line 248: / Line 272: @@
 ''No antineoplastic treatment prior to surgery.''
 ====Subsequent treatment====
 *[[Surgery#Gastrectomy|Surgery]]
 ===References===
-# '''EORTC 40954:''' Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010 Dec 10;28(35):5210-8. Epub 2010 Nov 8. [https://ascopubs.org/doi/10.1200/JCO.2009.26.6114 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020693/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21060024 PubMed]
+#'''EORTC 40954:''' Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010 Dec 10;28(35):5210-8. Epub 2010 Nov 8. [https://ascopubs.org/doi/10.1200/JCO.2009.26.6114 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020693/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21060024 PubMed]
 =Adjuvant therapy=
@@ Line 275: / Line 302: @@
 ''Note: Reported efficacy is based on the 2014 update.''
 ====Preceding treatment====
 *[[Surgery#Gastrectomy|Gastrectomy]] with D2 dissection
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
@@ Line 283: / Line 313: @@
 ===References===
-# '''CLASSIC:''' Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH; CLASSIC trial investigators. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012 Jan 28;379(9813):315-21. Epub 2012 Jan 7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61873-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22226517 PubMed]
-## '''Update:''' Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ; CLASSIC trial investigators. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1389-96. Epub 2014 Oct 15. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70473-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25439693 PubMed]
+#'''CLASSIC:''' Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH; CLASSIC trial investigators. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012 Jan 28;379(9813):315-21. Epub 2012 Jan 7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61873-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22226517 PubMed]
+##'''Update:''' Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ; CLASSIC trial investigators. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1389-96. Epub 2014 Oct 15. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70473-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25439693 PubMed]
 ==Carboplatin & Docetaxel {{#subobject:7263b8|Regimen=1}}==
@@ Line 306: / Line 337: @@
 ''Note: the original protocol was for cisplatin & docetaxel but was changed due to excess CINV. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 ====Preceding treatment====
 *[[Surgery#Gastrectomy|Surgery]]
 ====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
@@ Line 314: / Line 348: @@
 ===References===
-# Bamias A, Karina M, Papakostas P, Kostopoulos I, Bobos M, Vourli G, Samantas E, Christodoulou Ch, Pentheroudakis G, Pectasides D, Dimopoulos MA, Fountzilas G. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010 May;65(6):1009-21. Epub 2010 Feb 4. [https://link.springer.com/article/10.1007%2Fs00280-010-1256-6 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20130877 PubMed]
+#Bamias A, Karina M, Papakostas P, Kostopoulos I, Bobos M, Vourli G, Samantas E, Christodoulou Ch, Pentheroudakis G, Pectasides D, Dimopoulos MA, Fountzilas G. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010 May;65(6):1009-21. Epub 2010 Feb 4. [https://link.springer.com/article/10.1007%2Fs00280-010-1256-6 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20130877 PubMed]
 ==Cisplatin & Fluorouracil {{#subobject:7b88be|Regimen=1}}==
@@ Line 338: / Line 373: @@
 ''Study included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).''
 ====Preceding treatment====
 *[[#Cisplatin_.26_Fluorouracil|Neoadjuvant cisplatin & 5-FU]], then [[Surgery#Gastrectomy|surgery]]
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 28
 *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
@@ Line 346: / Line 384: @@
 ===References===
-# '''ACCORD 07:''' Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. [http://jco.ascopubs.org/content/29/13/1715.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21444866 PubMed]
+#'''ACCORD 07:''' Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. [http://jco.ascopubs.org/content/29/13/1715.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21444866 PubMed]
 ==CX {{#subobject:4896bc|Regimen=1}}==
@@ Line 370: / Line 409: @@
 ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm. This trial should not be confused for the one by the same name in colorectal cancer.''
 ====Preceding treatment====
 *R0 [[Surgery#Gastrectomy|gastrectomy]] and at least D2 dissection
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
@@ Line 379: / Line 420: @@
 ===References===
-# '''ARTIST:''' Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. Epub 2011 Dec 19. [http://jco.ascopubs.org/content/30/3/268.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22184384 PubMed]
-## '''Update:''' Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: Final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. Epub 2015 Jan 5. [http://jco.ascopubs.org/content/33/28/3130.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25559811 PubMed]
+#'''ARTIST:''' Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. Epub 2011 Dec 19. [http://jco.ascopubs.org/content/30/3/268.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22184384 PubMed]
+##'''Update:''' Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: Final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. Epub 2015 Jan 5. [http://jco.ascopubs.org/content/33/28/3130.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25559811 PubMed]
 ==ECF {{#subobject:f0281c|Regimen=1}}==
@@ Line 411: / Line 453: @@
 ====Preceding treatment====
 *[[#ECF|Neoadjuvant ECF]] x 3, then [[Surgery#Gastrectomy|surgery]]
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
@@ Line 418: / Line 463: @@
 ====Supportive medications====
 *MAGIC, suggested as thrombosis prophylaxis:
 **[[Warfarin (Coumadin)]] 1 mg PO once per day
@@ Line 424: / Line 470: @@
 ===References===
-# '''MAGIC:''' Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
-# '''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
+#'''MAGIC:''' Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
 ==ECX {{#subobject:4be711|Regimen=1}}==
@@ Line 447: / Line 494: @@
 |}
 ====Preceding treatment====
 *[[#ECX|ECX]] x 3, then [[Surgery#Gastrectomy|surgery]]
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
@@ Line 456: / Line 506: @@
 ===References===
-# '''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
 ==EOF {{#subobject:46c9e7|Regimen=1}}==
@@ Line 479: / Line 530: @@
 ''Only patients with trouble swallowing pills were assigned to this treatment arm.''
 ====Preceding treatment====
 *[[#EOF|EOF]] x 3, then [[Surgery#Gastrectomy|surgery]]
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
@@ Line 488: / Line 542: @@
 ===References===
-# '''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
 ==EOX {{#subobject:64769a|Regimen=1}}==
@@ Line 510: / Line 565: @@
 |}
 ====Preceding treatment====
 *[[#EOX|EOX]] x 3, then [[Surgery#Gastrectomy|surgery]]
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
@@ Line 519: / Line 577: @@
 ===References===
-# '''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30132-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29650363 PubMed]
 ==FLOT {{#subobject:3ad093|Regimen=1}}==
@@ Line 537: / Line 596: @@
 | style="background-color:#1a9851" |Phase II/III (E)
 |ECF/ECX [[Complex_multipart_regimens#FLOT4-AIO|See link]]
-|style="background-color:#91cf60"|Seems to have superior OS [[Complex_multipart_regimens#FLOT4-AIO|See link]]
+| style="background-color:#91cf60" |Seems to have superior OS [[Complex_multipart_regimens#FLOT4-AIO|See link]]
 |-
 |}
 ''This is the adjuvant portion of pre-planned perioperative chemotherapy.''
 ====Preceding treatment====
 *[[#FLOT|Neoadjuvant FLOT]] x 4, then [[Surgery#Gastrectomy|surgery]]
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 1
 *[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1
@@ Line 552: / Line 614: @@
 ===References===
-# '''FLOT4-AIO:''' Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30531-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27776843 PubMed]
-## '''Update:''' Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 Apr 10. [Epub ahead of print] [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32557-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30982686 PubMed]
+#'''FLOT4-AIO:''' Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30531-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27776843 PubMed]
+##'''Update:''' Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 Apr 10. [Epub ahead of print] [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32557-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30982686 PubMed]
 ==FP/Capecitabine & RT {{#subobject:778727|Regimen=1}}==
@@ Line 572: / Line 635: @@
 ''Note: In contrast to the primary reference, some guidelines list this regimen without FP cycles 1, 3, 4, 5. Dosage of [[Capecitabine (Xeloda)]] was listed as 625 to 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5 or 1 to 7 while radiation is being given.''
 ====Preceding treatment====
 *[[Surgery#Gastrectomy|Surgery]], 3 weeks prior
 ====Chemotherapy, part 1====
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 5000 mg/m<sup>2</sup>)
@@ Line 580: / Line 646: @@
 ====Chemotherapy, part 2====
 *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day
 ====Radiotherapy====
 *Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.8 Gy fractions x 25 fractions (total dose of 45 Gy)
@@ Line 587: / Line 656: @@
 ====Chemotherapy, part 3====
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m<sup>2</sup>)
@@ Line 593: / Line 663: @@
 ===References===
-# Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH, Kim JS, Lee JH, Jung GJ, Kim MC. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol. 2006 Jan 28;12(4):603-7. [http://www.wjgnet.com/1007-9327/full/v12/i4/603.htm link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066094/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/16489675 PubMed]
+#Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH, Kim JS, Lee JH, Jung GJ, Kim MC. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol. 2006 Jan 28;12(4):603-7. [http://www.wjgnet.com/1007-9327/full/v12/i4/603.htm link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066094/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/16489675 PubMed]
 ==FULV/FULV & RT {{#subobject:2cd29|Regimen=1}}==
@@ Line 623: / Line 694: @@
 ''Study included patients with GE junction malignancy as well (20% GE junction) and included patients with a performance status of 2.''
 ====Preceding treatment====
 *INT-0116: [[Surgery#Gastrectomy|Surgery]] with R0 resection (10% underwent D2 dissection, 36% underwent D1 dissection and 54% underwent D0 dissection)
 *CALGB 80101: [[Surgery#Gastrectomy|Surgery]]
 ====Chemotherapy, part 1====
 *[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 *[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
@@ Line 632: / Line 706: @@
 ====Chemotherapy, part 2====
 *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
 *[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
 ====Radiotherapy====
 *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy x 25 fractions (total of 45 Gy)
@@ Line 640: / Line 717: @@
 ====Chemotherapy, part 3====
 *[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 *[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
@@ Line 645: / Line 723: @@
 '''28-day cycle for 2 cycles'''
 ===References===
-# '''INT-0116:''' Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [https://www.nejm.org/doi/full/10.1056/NEJMoa010187 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11547741 PubMed]
-## '''Update:''' Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.7136 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517071/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585691 PubMed]
+#'''INT-0116:''' Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [https://www.nejm.org/doi/full/10.1056/NEJMoa010187 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11547741 PubMed]
-# '''CALGB 80101:''' Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, Enzinger PC, Haller DG, Dragovich T, Alberts SR, Bjarnason GA, Willett CG, Gunderson LL, Goldberg RM, Venook AP, Ilson D, O'Reilly E, Ciombor K, Berg DJ, Meyerhardt J, Mayer RJ. Adjuvant chemoradiotherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: results from CALGB 80101 (Alliance). J Clin Oncol. 2017 Nov 10;35(32):3671-3677. Epub 2017 Oct 4. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.2130 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678342/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28976791 PubMed]
+##'''Update:''' Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.7136 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517071/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585691 PubMed]
+#'''CALGB 80101:''' Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, Enzinger PC, Haller DG, Dragovich T, Alberts SR, Bjarnason GA, Willett CG, Gunderson LL, Goldberg RM, Venook AP, Ilson D, O'Reilly E, Ciombor K, Berg DJ, Meyerhardt J, Mayer RJ. Adjuvant chemoradiotherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: results from CALGB 80101 (Alliance). J Clin Oncol. 2017 Nov 10;35(32):3671-3677. Epub 2017 Oct 4. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.2130 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678342/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28976791 PubMed]
 ==Observation==
@@ Line 749: / Line 828: @@
 ''No further treatment after surgery.''
 ====Preceding treatment====
 *[[Surgery#Gastrectomy|Surgery]], with varying requirements for level of dissection (see papers for details)
 ===References===
-# Allum WH, Hallissey MT, Kelly KA; British Stomach Cancer Group. Adjuvant chemotherapy in operable gastric cancer: 5 year follow-up of first British Stomach Cancer Group trial. Lancet. 1989 Mar 18;1(8638):571-4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(89)91607-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2564109 PubMed]
-# Coombes RC, Schein PS, Chilvers CE, Wils J, Beretta G, Bliss JM, Rutten A, Amadori D, Cortes-Funes H, Villar-Grimalt A, McArdle C, Rauschecker HF, Boven E, Vassilopoulos P, Welvaart K, Pinto Ferreira E, Wiig J, Gisselbrecht C, Rougier P, Woods EMA; International Collaborative Cancer Group. A randomized trial comparing adjuvant fluorouracil, doxorubicin, and mitomycin with no treatment in operable gastric cancer. J Clin Oncol. 1990 Aug;8(8):1362-9. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.8.1362 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2199622 PubMed]
-# Hallissey MT, Dunn JA, Ward LC, Allum WH; British Stomach Cancer Group. The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up. Lancet. 1994 May 28;343(8909):1309-12. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(94)92464-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7910321 PubMed]
-# '''EORTC 40813:''' Lise M, Nitti D, Marchet A, Sahmoud T, Buyse M, Duez N, Fiorentino M, Dos Santos JG, Labianca R, Rougier P, Gignoux M. Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer. J Clin Oncol. 1995 Nov;13(11):2757-63. [https://ascopubs.org/doi/abs/10.1200/JCO.1995.13.11.2757 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7595735 PubMed]
-# Macdonald JS, Fleming TR, Peterson RF, Berenberg JL, McClure S, Chapman RA, Eyre HJ, Solanki D, Cruz AB Jr, Gagliano R, Estes NC, Tangen CM, Rivkin S. Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A Southwest Oncology Group study. Ann Surg Oncol. 1995 Nov;2(6):488-94. [https://link.springer.com/article/10.1007/BF02307081 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8591078 PubMed]
-# '''JCOG8801:''' Nakajima T, Nashimoto A, Kitamura M, Kito T, Iwanaga T, Okabayashi K, Goto M; Gastric Cancer Surgical Study Group. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Lancet. 1999 Jul 24;354(9175):273-7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)01048-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10440302 PubMed]
-# Cirera L, Balil A, Batiste-Alentorn E, Tusquets I, Cardona T, Arcusa A, Jolis L, Saigí E, Guasch I, Badia A, Boleda M. Randomized clinical trial of adjuvant mitomycin plus tegafur in patients with resected stage III gastric cancer. J Clin Oncol. 1999 Dec;17(12):3810-5. [https://ascopubs.org/doi/full/10.1200/JCO.1999.17.12.3810 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10577853 PubMed]
-# '''INT-0116:''' Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [https://www.nejm.org/doi/full/10.1056/NEJMoa010187 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11547741 PubMed]
-## '''Update:''' Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.7136 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517071/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585691 PubMed]
-# '''JCOG 9206-1:''' Nashimoto A, Nakajima T, Furukawa H, Kitamura M, Kinoshita T, Yamamura Y, Sasako M, Kunii Y, Motohashi H, Yamamoto S; Gastric Cancer Surgical Study Group, Japan Clinical Oncology Group. Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1. J Clin Oncol. 2003 Jun 15;21(12):2282-7. [https://ascopubs.org/doi/full/10.1200/JCO.2003.06.103 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12805327 PubMed]
-# '''FFCD 8801:''' Bouché O, Ychou M, Burtin P, Bedenne L, Ducreux M, Lebreton G, Baulieux J, Nordlinger B, Martin C, Seitz JF, Tigaud JM, Echinard E, Stremsdoerfer N, Milan C, Rougier P; Fédération Francophone de Cancérologie Digestive Group. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol. 2005 Sep;16(9):1488-97. Epub 2005 Jun 6. [https://academic.oup.com/annonc/article/16/9/1488/180180 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15939717 PubMed]
-# Nitti D, Wils J, Dos Santos JG, Fountzilas G, Conte PF, Sava C, Tres A, Coombes RC, Crivellari D, Marchet A, Sanchez E, Bliss JM, Homewood J, Couvreur ML, Hall E, Baron B, Woods E, Emson M, Van Cutsem E, Lise M; EORTC GI Group; ICCG. Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer: a combined analysis of the EORTC GI Group and the ICCG. Ann Oncol. 2006 Feb;17(2):262-9. Epub 2005 Nov 17. [https://academic.oup.com/annonc/article/17/2/262/165316 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293676 PubMed]
-# '''MAGIC:''' Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
-# '''GOIM 9602:''' De Vita F, Giuliani F, Orditura M, Maiello E, Galizia G, Di Martino N, Montemurro F, Cartenì G, Manzione L, Romito S, Gebbia V, Ciardiello F, Catalano G, Colucci G; Gruppo Oncologico Italia Meridionale. Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study). Ann Oncol. 2007 Aug;18(8):1354-8. Epub 2007 May 24. [https://academic.oup.com/annonc/article/18/8/1354/178453 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17525087 PubMed]
-# '''ACTS-GC:''' Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. [https://www.nejm.org/doi/full/10.1056/NEJMoa072252 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17978289 PubMed]
-## '''Update:''' Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.5908 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22010012 PubMed]
-# Di Costanzo F, Gasperoni S, Manzione L, Bisagni G, Labianca R, Bravi S, Cortesi E, Carlini P, Bracci R, Tomao S, Messerini L, Arcangeli A, Torri V, Bilancia D, Floriani I, Tonato M; Italian Oncology Group for Cancer Research. Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC. J Natl Cancer Inst. 2008 Mar 19;100(6):388-98. Epub 2008 Mar 11. [https://academic.oup.com/jnci/article/100/6/388/997958 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18334706 PubMed]
-# Kulig J, Kolodziejczyk P, Sierzega M, Bobrzynski L, Jedrys J, Popiela T, Dadan J, Drews M, Jeziorski A, Krawczyk M, Starzynska T, Wallner G. Adjuvant chemotherapy with etoposide, adriamycin and cisplatin compared with surgery alone in the treatment of gastric cancer: a phase III randomized, multicenter, clinical trial. Oncology. 2010;78(1):54-61. Epub 2010 Mar 6. [https://www.karger.com/Article/Abstract/292360 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20215786 PubMed]
-# '''JCOG 9206-2:''' Miyashiro I, Furukawa H, Sasako M, Yamamoto S, Nashimoto A, Nakajima T, Kinoshita T, Kobayashi O, Arai K; Gastric Cancer Surgical Study Group in the Japan Clinical Oncology Group. Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2. Gastric Cancer. 2011 Aug;14(3):212-8. Epub 2011 Feb 19. [https://link.springer.com/article/10.1007%2Fs10120-011-0027-3 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21336855 PubMed]
-==S-1 monotherapy {{#subobject:ec10ef|Regimen=1}}==
+#Allum WH, Hallissey MT, Kelly KA; British Stomach Cancer Group. Adjuvant chemotherapy in operable gastric cancer: 5 year follow-up of first British Stomach Cancer Group trial. Lancet. 1989 Mar 18;1(8638):571-4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(89)91607-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2564109 PubMed]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+#Coombes RC, Schein PS, Chilvers CE, Wils J, Beretta G, Bliss JM, Rutten A, Amadori D, Cortes-Funes H, Villar-Grimalt A, McArdle C, Rauschecker HF, Boven E, Vassilopoulos P, Welvaart K, Pinto Ferreira E, Wiig J, Gisselbrecht C, Rougier P, Woods EMA; International Collaborative Cancer Group. A randomized trial comparing adjuvant fluorouracil, doxorubicin, and mitomycin with no treatment in operable gastric cancer. J Clin Oncol. 1990 Aug;8(8):1362-9. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.8.1362 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2199622 PubMed]
-|-
+#Hallissey MT, Dunn JA, Ward LC, Allum WH; British Stomach Cancer Group. The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up. Lancet. 1994 May 28;343(8909):1309-12. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(94)92464-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7910321 PubMed]
-|[[#top|back to top]]
+#'''EORTC 40813:''' Lise M, Nitti D, Marchet A, Sahmoud T, Buyse M, Duez N, Fiorentino M, Dos Santos JG, Labianca R, Rougier P, Gignoux M. Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer. J Clin Oncol. 1995 Nov;13(11):2757-63. [https://ascopubs.org/doi/abs/10.1200/JCO.1995.13.11.2757 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7595735 PubMed]
+#Macdonald JS, Fleming TR, Peterson RF, Berenberg JL, McClure S, Chapman RA, Eyre HJ, Solanki D, Cruz AB Jr, Gagliano R, Estes NC, Tangen CM, Rivkin S. Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A Southwest Oncology Group study. Ann Surg Oncol. 1995 Nov;2(6):488-94. [https://link.springer.com/article/10.1007/BF02307081 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8591078 PubMed]
+#'''JCOG8801:''' Nakajima T, Nashimoto A, Kitamura M, Kito T, Iwanaga T, Okabayashi K, Goto M; Gastric Cancer Surgical Study Group. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Lancet. 1999 Jul 24;354(9175):273-7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)01048-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10440302 PubMed]
+#Cirera L, Balil A, Batiste-Alentorn E, Tusquets I, Cardona T, Arcusa A, Jolis L, Saigí E, Guasch I, Badia A, Boleda M. Randomized clinical trial of adjuvant mitomycin plus tegafur in patients with resected stage III gastric cancer. J Clin Oncol. 1999 Dec;17(12):3810-5. [https://ascopubs.org/doi/full/10.1200/JCO.1999.17.12.3810 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10577853 PubMed]
+#'''INT-0116:''' Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [https://www.nejm.org/doi/full/10.1056/NEJMoa010187 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11547741 PubMed]
+##'''Update:''' Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.7136 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517071/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22585691 PubMed]
+#'''JCOG 9206-1:''' Nashimoto A, Nakajima T, Furukawa H, Kitamura M, Kinoshita T, Yamamura Y, Sasako M, Kunii Y, Motohashi H, Yamamoto S; Gastric Cancer Surgical Study Group, Japan Clinical Oncology Group. Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1. J Clin Oncol. 2003 Jun 15;21(12):2282-7. [https://ascopubs.org/doi/full/10.1200/JCO.2003.06.103 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12805327 PubMed]
+#'''FFCD 8801:''' Bouché O, Ychou M, Burtin P, Bedenne L, Ducreux M, Lebreton G, Baulieux J, Nordlinger B, Martin C, Seitz JF, Tigaud JM, Echinard E, Stremsdoerfer N, Milan C, Rougier P; Fédération Francophone de Cancérologie Digestive Group. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol. 2005 Sep;16(9):1488-97. Epub 2005 Jun 6. [https://academic.oup.com/annonc/article/16/9/1488/180180 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15939717 PubMed]
+#Nitti D, Wils J, Dos Santos JG, Fountzilas G, Conte PF, Sava C, Tres A, Coombes RC, Crivellari D, Marchet A, Sanchez E, Bliss JM, Homewood J, Couvreur ML, Hall E, Baron B, Woods E, Emson M, Van Cutsem E, Lise M; EORTC GI Group; ICCG. Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer: a combined analysis of the EORTC GI Group and the ICCG. Ann Oncol. 2006 Feb;17(2):262-9. Epub 2005 Nov 17. [https://academic.oup.com/annonc/article/17/2/262/165316 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293676 PubMed]
+#'''MAGIC:''' Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
+#'''GOIM 9602:''' De Vita F, Giuliani F, Orditura M, Maiello E, Galizia G, Di Martino N, Montemurro F, Cartenì G, Manzione L, Romito S, Gebbia V, Ciardiello F, Catalano G, Colucci G; Gruppo Oncologico Italia Meridionale. Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study). Ann Oncol. 2007 Aug;18(8):1354-8. Epub 2007 May 24. [https://academic.oup.com/annonc/article/18/8/1354/178453 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17525087 PubMed]
+#'''ACTS-GC:''' Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. [https://www.nejm.org/doi/full/10.1056/NEJMoa072252 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17978289 PubMed]
+##'''Update:''' Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.5908 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22010012 PubMed]
+#Di Costanzo F, Gasperoni S, Manzione L, Bisagni G, Labianca R, Bravi S, Cortesi E, Carlini P, Bracci R, Tomao S, Messerini L, Arcangeli A, Torri V, Bilancia D, Floriani I, Tonato M; Italian Oncology Group for Cancer Research. Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC. J Natl Cancer Inst. 2008 Mar 19;100(6):388-98. Epub 2008 Mar 11. [https://academic.oup.com/jnci/article/100/6/388/997958 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18334706 PubMed]
+#Kulig J, Kolodziejczyk P, Sierzega M, Bobrzynski L, Jedrys J, Popiela T, Dadan J, Drews M, Jeziorski A, Krawczyk M, Starzynska T, Wallner G. Adjuvant chemotherapy with etoposide, adriamycin and cisplatin compared with surgery alone in the treatment of gastric cancer: a phase III randomized, multicenter, clinical trial. Oncology. 2010;78(1):54-61. Epub 2010 Mar 6. [https://www.karger.com/Article/Abstract/292360 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20215786 PubMed]
+#'''JCOG 9206-2:''' Miyashiro I, Furukawa H, Sasako M, Yamamoto S, Nashimoto A, Nakajima T, Kinoshita T, Kobayashi O, Arai K; Gastric Cancer Surgical Study Group in the Japan Clinical Oncology Group. Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2. Gastric Cancer. 2011 Aug;14(3):212-8. Epub 2011 Feb 19. [https://link.springer.com/article/10.1007%2Fs10120-011-0027-3 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21336855 PubMed]
+== Pembrolizumab Monotherapy ==
+{| class="wikitable"
+|[[Gastric cancer#top|back to top]]
 |}
-===Variant #1, 21-day cycles {{#subobject:5dbc53|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
+=== Regimen ===
-! style="width: 25%" |Study
+{| class="wikitable"
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!Study
-! style="width: 25%" |Comparator
+![[Levels of Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+!Comparator
-|-
+![[Levels of Evidence#Efficacy|Efficacy]]
-| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70025-7/fulltext Tsuburaya (SAMIT)]
-| rowspan="2" style="background-color:#1a9851" |Phase III (C)
-|1. Paclitaxel, then S-1<br> 2. Paclitaxel, then UFT
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|3. UFT
-| style="background-color:#1a9850" |Superior DFS
 |-
+|Tabernero et. al, 2019 (KEYNOTE-062)
+|Randomized Phase III
+|Chemotherapy
+|May be superior
 |}
-====Preceding treatment====
+''KEYNOTE-062 included patients with GEJ malignancy''
-*R0 or R1 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection, within 2 to 8 weeks
-====Chemotherapy====
+''*Improved OS was seen in patients with PD-L1 CPS score of 10 or more (HR: 0.62) but was not tested per analysis plan''
-*[[Tegafur, gimeracil, oteracil (S-1)]] 80 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+==== Chemotherapy ====
+* Pembrolizumab (Keytruda) 200 mg IV daily on day 1
+'''21-day cycles'''
+=== References ===
+# '''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. DOI: 10.1200/JCO.2019.37.18_suppl.LBA4007  37, no. 18_suppl
+== Pembrolizumab + Cisplatin + 5-FU ==
+{| class="wikitable"
+|[[Gastric cancer#top|back to top]]
+|}
+=== Regimen ===
+{| class="wikitable"
+!Study
+![[Levels of Evidence#Evidence|Evidence]]
+!Comparator
+![[Levels of Evidence#Efficacy|Efficacy]]
+|-
+|Tabernero et. al, 2019 (KEYNOTE-062)
+|Randomized Phase III
+|Cisplatin + 5-FU + Placebo
+|Inferior OS
+|}
+''KEYNOTE-062 included patients with GEJ malignancy''
+==== Chemotherapy ====
+* Pembrolizumab (Keytruda) 200 mg IV daily on day 1
+* Cisplatin 80 mg/m<sup>2</sup> on day 1
+* 5-FU 800 mg/m<sup>2</sup> on days 1-5 OR capecitabine 1000 mg/m<sup>2</sup> PO BID on days 1-14
+'''21-day cycles'''
+=== References ===
-'''21-day cycle for 16 cycles'''
+# '''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. DOI: 10.1200/JCO.2019.37.18_suppl.LBA4007  37, no. 18_suppl
-===Variant #2, 42-day cycles {{#subobject:0ee98c|Variant=1}}===
+==S-1 monotherapy {{#subobject:ec10ef|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Variant #1, 21-day cycles {{#subobject:5dbc53|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
 ! style="width: 25%" |Study
@@ Line 807: / Line 927: @@
 ! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa072252 Sakuramoto et al. 2007 (ACTS-GC)]
+| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70025-7/fulltext Tsuburaya (SAMIT)]
-| style="background-color:#1a9851" |Phase III (E)
+| rowspan="2" style="background-color:#1a9851" |Phase III (C)
+|1. Paclitaxel, then S-1<br> 2. Paclitaxel, then UFT
+| style="background-color:#ffffbf" |Seems not superior
+|-
+|3. UFT
+| style="background-color:#1a9850" |Superior DFS
+|-
+|}
+====Preceding treatment====
+*R0 or R1 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection, within 2 to 8 weeks
+====Chemotherapy====
+*[[Tegafur, gimeracil, oteracil (S-1)]] 80 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+'''21-day cycle for 16 cycles'''
+===Variant #2, 42-day cycles {{#subobject:0ee98c|Variant=1}}===
+{| class="wikitable" style="width: 100%; text-align:center;"
+! style="width: 25%" |Study
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |Comparator
+! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+|-
+|[https://www.nejm.org/doi/full/10.1056/NEJMoa072252 Sakuramoto et al. 2007 (ACTS-GC)]
+| style="background-color:#1a9851" |Phase III (E)
 |[[#Observation|Observation]]
 | style="background-color:#1a9850" |Superior OS
@@ Line 819: / Line 965: @@
 |}
 ====Preceding treatment====
 *R0 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection, within 6 weeks
 ====Chemotherapy====
 *[[Tegafur, gimeracil, oteracil (S-1)]] as follows:
 **BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
@@ Line 828: / Line 977: @@
 '''42-day cycle for 8 cycles'''
 ===References===
-# '''ACTS-GC:''' Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. [https://www.nejm.org/doi/full/10.1056/NEJMoa072252 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17978289 PubMed]
-## '''Update:''' Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.5908 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22010012 PubMed]
+#'''ACTS-GC:''' Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. [https://www.nejm.org/doi/full/10.1056/NEJMoa072252 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17978289 PubMed]
-# '''SAMIT:''' Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, Tanabe K, Takahashi N, Imamura H, Tatsumoto N, Hara A, Nishikawa K, Fukushima R, Nozaki I, Kojima H, Miyashita Y, Oba K, Buyse M, Morita S, Sakamoto J. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):886-93. Epub 2014 Jun 18. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70025-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24954805 PubMed]
+##'''Update:''' Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.5908 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22010012 PubMed]
-# '''OPAS-1:''' Yoshikawa T, Terashima M, Mizusawa J, Nunobe S, Nishida Y, Yamada T, Kaji M, Fukushima N, Hato S, Choda Y, Yabusaki H, Yoshida K, Ito S, Takeno A, Yasuda T, Kawachi Y, Katayama H, Fukuda H, Boku N, Sano T, Sasako M. Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104[OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol. 2019 Mar;4(3):208-216. Epub 2019 Jan 22. Erratum in: Lancet Gastroenterol Hepatol. 2019 Apr;4(4):e3. [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(18)30383-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30679107 PubMed]
+#'''SAMIT:''' Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, Tanabe K, Takahashi N, Imamura H, Tatsumoto N, Hara A, Nishikawa K, Fukushima R, Nozaki I, Kojima H, Miyashita Y, Oba K, Buyse M, Morita S, Sakamoto J. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):886-93. Epub 2014 Jun 18. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70025-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24954805 PubMed]
+#'''OPAS-1:''' Yoshikawa T, Terashima M, Mizusawa J, Nunobe S, Nishida Y, Yamada T, Kaji M, Fukushima N, Hato S, Choda Y, Yabusaki H, Yoshida K, Ito S, Takeno A, Yasuda T, Kawachi Y, Katayama H, Fukuda H, Boku N, Sano T, Sasako M. Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104[OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol. 2019 Mar;4(3):208-216. Epub 2019 Jan 22. Erratum in: Lancet Gastroenterol Hepatol. 2019 Apr;4(4):e3. [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(18)30383-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30679107 PubMed]
 =Metastatic or locally advanced disease, first-line=
@@ Line 854: / Line 1,004: @@
 |}
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
@@ Line 869: / Line 1,020: @@
 ''Study only included patients with Karnofsky status of at least 70%''
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
@@ Line 874: / Line 1,026: @@
 ===References===
-# Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. [http://annonc.oxfordjournals.org/content/15/9/1344.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15319239 PubMed]
-# Hwang IG, Ji JH, Kang JH, Lee HR, Lee HY, Chi KC, Park SW, Lee SJ, Kim ST, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK. A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer. J Geriatr Oncol. 2017 May;8(3):170-175. Epub 2017 Jan 21. [https://www.geriatriconcology.net/article/S1879-4068(17)30022-X/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28119041 PubMed]
+#Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. [http://annonc.oxfordjournals.org/content/15/9/1344.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15319239 PubMed]
+#Hwang IG, Ji JH, Kang JH, Lee HR, Lee HY, Chi KC, Park SW, Lee SJ, Kim ST, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK. A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer. J Geriatr Oncol. 2017 May;8(3):170-175. Epub 2017 Jan 21. [https://www.geriatriconcology.net/article/S1879-4068(17)30022-X/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28119041 PubMed]
 ==CapeOx {{#subobject:4e3bb4|Regimen=1}}==
@@ Line 893: / Line 1,046: @@
 |}
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 850 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
@@ Line 899: / Line 1,053: @@
 ===References===
-# Jatoi A, Murphy BR, Foster NR, Nikcevich DA, Alberts SR, Knost JA, Fitch TR, Rowland KM Jr; North Central Cancer Treatment Group. Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. Ann Oncol. 2006 Jan;17(1):29-34. Epub 2005 Nov 22. [https://academic.oup.com/annonc/article/17/1/29/161212 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16303863 PubMed]
+#Jatoi A, Murphy BR, Foster NR, Nikcevich DA, Alberts SR, Knost JA, Fitch TR, Rowland KM Jr; North Central Cancer Treatment Group. Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. Ann Oncol. 2006 Jan;17(1):29-34. Epub 2005 Nov 22. [https://academic.oup.com/annonc/article/17/1/29/161212 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16303863 PubMed]
 ==Carboplatin & Paclitaxel {{#subobject:4df570|Regimen=1}}==
@@ Line 924: / Line 1,079: @@
 ''Gadgeel et al. study showed an ORR of 35%''
 ====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1, '''given second'''
 *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
@@ Line 930: / Line 1,086: @@
 ===References===
-# Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9427274 PubMed]
-# Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003 Feb;26(1):37-41. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12576922 PubMed]
+#Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9427274 PubMed]
+#Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003 Feb;26(1):37-41. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12576922 PubMed]
 ==Cisplatin & Docetaxel {{#subobject:724868|Regimen=1}}==
@@ Line 959: / Line 1,116: @@
 ''Note: the protocol was amended to change the original dose of docetaxel from 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 ====Supportive medications====
 *3 liters per day "hyperhydration"
 *[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO twice per day for 4 days after [[Docetaxel (Taxotere)]]
@@ Line 986: / Line 1,145: @@
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
 *[[Docetaxel (Taxotere)]] 85 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 ====Supportive medications====
 *[[Dexamethasone (Decadron)]] 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (total dose per cycle: 48 mg)
 *[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
@@ Line 998: / Line 1,159: @@
 ===References===
-# '''V-325:''' Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [http://jco.ascopubs.org/content/23/24/5660.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16110025 PubMed]
-# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
+#'''V-325:''' Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [http://jco.ascopubs.org/content/23/24/5660.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16110025 PubMed]
+#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
 ==Cisplatin & Fluorouracil {{#subobject:4d9936|Regimen=1}}==
@@ Line 1,026: / Line 1,188: @@
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
 *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
 ====Supportive medications====
 *Some protocols: "Hyperhydration" for [[Cisplatin (Platinol)]]
@@ Line 1,048: / Line 1,212: @@
 |}
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
 *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
 ====Supportive medications====
 *Some protocols: "Hyperhydration" for [[Cisplatin (Platinol)]]
@@ Line 1,070: / Line 1,236: @@
 |}
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
 *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
 ====Supportive medications====
 *Some protocols: "Hyperhydration" for [[Cisplatin (Platinol)]]
@@ Line 1,092: / Line 1,260: @@
 |}
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on either day 1 or 2
 *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
@@ Line 1,116: / Line 1,285: @@
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
 *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
@@ Line 1,149: / Line 1,319: @@
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
 *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 5000 mg/m<sup>2</sup> )
 ====Supportive medications====
 *As described in Dank et al. 2008:
 *"Hyperhydration" for 2 to 3 days with each infusion
@@ Line 1,159: / Line 1,331: @@
 *[[Metoclopramide (Reglan)]] for antiemetic prophylaxis
 *[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting on day 4, to be continued until ANC greater than 1000/uL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
 *[[Atropine (Atropen)]] prn cholinergic symptoms
 *[[Loperamide (Imodium)]] prn delayed diarrhea
 '''28-day cycles'''
 ===References===
-# '''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
-# '''FFCD 9404:''' Duffour J, Bouché O, Rougier P, Milan C, Bedenne L, Seitz JF, Buecher B, Legoux JL, Ducreux M, Vetter D, Raoul JL, François E, Ychou M. Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial). Anticancer Res. 2006 Sep-Oct;26(5B):3877-83. [http://ar.iiarjournals.org/content/26/5B/3877.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17094417 PubMed]
+#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
-# '''TAX 325:''' Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [http://jco.ascopubs.org/content/24/31/4991.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17075117 PubMed]
+#'''FFCD 9404:''' Duffour J, Bouché O, Rougier P, Milan C, Bedenne L, Seitz JF, Buecher B, Legoux JL, Ducreux M, Vetter D, Raoul JL, François E, Ychou M. Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial). Anticancer Res. 2006 Sep-Oct;26(5B):3877-83. [http://ar.iiarjournals.org/content/26/5B/3877.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17094417 PubMed]
-# Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [http://annonc.oxfordjournals.org/content/19/8/1450.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18558665 PubMed]
+#'''TAX 325:''' Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [http://jco.ascopubs.org/content/24/31/4991.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17075117 PubMed]
-# Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [http://annonc.oxfordjournals.org/content/20/4/666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19153121 PubMed]
+#Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [http://annonc.oxfordjournals.org/content/19/8/1450.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18558665 PubMed]
-# '''FLAGS:''' Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. [https://ascopubs.org/doi/10.1200/JCO.2009.25.4706 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20159816 PubMed]
+#Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [http://annonc.oxfordjournals.org/content/20/4/666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19153121 PubMed]
-# '''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
+#'''FLAGS:''' Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. [https://ascopubs.org/doi/10.1200/JCO.2009.25.4706 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20159816 PubMed]
-# '''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.2236 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21844504 PubMed]
+#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
-# '''DIGEST:''' Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. [https://academic.oup.com/annonc/article/28/9/2142/4061259 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28911091 PubMed]
+#'''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.2236 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21844504 PubMed]
+#'''DIGEST:''' Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. [https://academic.oup.com/annonc/article/28/9/2142/4061259 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28911091 PubMed]
 ==Cisplatin & S-1 {{#subobject:252c51|Regimen=1}}==
@@ Line 1,195: / Line 1,368: @@
 |}
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 *[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 14
@@ Line 1,220: / Line 1,394: @@
 ''Note: this is an experimental arm of a study where the primary endpoint was not met. Included because CS has been shown to be superior in comparison to other regimens (see above).''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
 *[[Tegafur, gimeracil, oteracil (S-1)]] 25 mg/m<sup>2</sup> PO twice per day on days 1 to 21
@@ Line 1,271: / Line 1,446: @@
 ''Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details''
 ====Preceding treatment====
 *REGATTA: Non-laparoscopic [[Surgery#Gastrectomy|gastrectomy]] with D1 [[Surgery#Lymphadenectomy|lymphadenectomy]] versus no surgery; chemotherapy began within 8 weeks of surgery
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 8
 *[[Tegafur, gimeracil, oteracil (S-1)]] as follows:
@@ Line 1,283: / Line 1,460: @@
 ===References===
-# '''SPIRITS:''' Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70035-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18282805 PubMed]
-# '''FLAGS:''' Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. [https://ascopubs.org/doi/10.1200/JCO.2009.25.4706 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20159816 PubMed]
+#'''SPIRITS:''' Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70035-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18282805 PubMed]
-# '''G-SOX:''' Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hamada C, Hyodo I. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015 Jan;26(1):141-8. Epub 2014 Oct 14. [https://academic.oup.com/annonc/article/26/1/141/2802628 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25316259 PubMed]
+#'''FLAGS:''' Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. [https://ascopubs.org/doi/10.1200/JCO.2009.25.4706 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20159816 PubMed]
-# '''SOS:''' Ryu MH, Baba E, Lee KH, Park YI, Boku N, Hyodo I, Nam BH, Esaki T, Yoo C, Ryoo BY, Song EK, Cho SH, Kang WK, Yang SH, Zang DY, Shin DB, Park SR, Shinozaki K, Takano T, Kang YK; SOS study investigators. Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS). Ann Oncol. 2015 Oct;26(10):2097-101. Epub 2015 Jul 27. [https://academic.oup.com/annonc/article/26/10/2097/144476 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26216386 PubMed]
+#'''G-SOX:''' Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hamada C, Hyodo I. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015 Jan;26(1):141-8. Epub 2014 Oct 14. [https://academic.oup.com/annonc/article/26/1/141/2802628 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25316259 PubMed]
-# '''REGATTA:''' Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. Epub 2016 Jan 26. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00553-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26822397 PubMed]
+#'''SOS:''' Ryu MH, Baba E, Lee KH, Park YI, Boku N, Hyodo I, Nam BH, Esaki T, Yoo C, Ryoo BY, Song EK, Cho SH, Kang WK, Yang SH, Zang DY, Shin DB, Park SR, Shinozaki K, Takano T, Kang YK; SOS study investigators. Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS). Ann Oncol. 2015 Oct;26(10):2097-101. Epub 2015 Jul 27. [https://academic.oup.com/annonc/article/26/10/2097/144476 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26216386 PubMed]
-# '''DIGEST:''' Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. [https://academic.oup.com/annonc/article/28/9/2142/4061259 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28911091 PubMed]
+#'''REGATTA:''' Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. Epub 2016 Jan 26. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00553-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26822397 PubMed]
-# '''PHOENIX-GC:''' Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. [https://ascopubs.org/doi/full/10.1200/JCO.2018.77.8613 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29746229 PubMed]
+#'''DIGEST:''' Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. [https://academic.oup.com/annonc/article/28/9/2142/4061259 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28911091 PubMed]
-# '''JCOG1013:''' Yamada Y, Boku N, Mizusawa J, Iwasa S, Kadowaki S, Nakayama N, Azuma M, Sakamoto T, Shitara K, Tamura T, Chin K, Hata H, Nakamori M, Hara H, Yasui H, Katayama H, Fukuda H, Yoshikawa T, Sasako M, Terashima M. Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 May 14. [Epub ahead of print] [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(19)30083-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31101534 PubMed]
+#'''PHOENIX-GC:''' Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. [https://ascopubs.org/doi/full/10.1200/JCO.2018.77.8613 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29746229 PubMed]
+#'''JCOG1013:''' Yamada Y, Boku N, Mizusawa J, Iwasa S, Kadowaki S, Nakayama N, Azuma M, Sakamoto T, Shitara K, Tamura T, Chin K, Hata H, Nakamori M, Hara H, Yasui H, Katayama H, Fukuda H, Yoshikawa T, Sasako M, Terashima M. Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 May 14. [Epub ahead of print] [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(19)30083-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31101534 PubMed]
 ==CLF {{#subobject:b913d6|Regimen=1}}==
@@ Line 1,316: / Line 1,494: @@
 ''Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric'').
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
 *[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
@@ Line 1,321: / Line 1,500: @@
 ====Supportive medications====
 *Up to 3 liters normal saline as hydration with [[Cisplatin (Platinol)]]
 *Antiemetic medications per "local protocols"
@@ Line 1,341: / Line 1,521: @@
 ''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more regular schedule was used.''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on either day 1 or 2
 *[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
@@ Line 1,346: / Line 1,527: @@
 ====Supportive medications====
 *1 liter hydration over 3 hours before and after [[Cisplatin (Platinol)]]
 *[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV before [[Cisplatin (Platinol)]]
@@ Line 1,354: / Line 1,536: @@
 ===References===
-# '''FFCD 9803:''' Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [http://jco.ascopubs.org/content/22/21/4319.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15514373 PubMed]
-# Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [http://jco.ascopubs.org/content/26/9/1435.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18349393 PubMed]
+#'''FFCD 9803:''' Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [http://jco.ascopubs.org/content/22/21/4319.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15514373 PubMed]
+#Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [http://jco.ascopubs.org/content/26/9/1435.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18349393 PubMed]
 ==CX {{#subobject:2bd34d|Regimen=1}}==
@@ Line 1,408: / Line 1,591: @@
 |}
 The following studies included patients with GE junction malignancy as well:
-* ''AVAGAST patients: 86% gastric and 14% GE junction. 5.4% of patients had an ECOG of 2.''
-* ''EXPAND patients: 83% gastric, 5% GE junction and 16% unknown''
+*''AVAGAST patients: 86% gastric and 14% GE junction. 5.4% of patients had an ECOG of 2.''
-* ''Kim et al patients: 79% gastric, 16% GE junction and 5% unknown''
+*''EXPAND patients: 83% gastric, 5% GE junction and 16% unknown''
+*''Kim et al patients: 79% gastric, 16% GE junction and 5% unknown''
 ''Note: while the primary analysis of RAINFALL showed that this arm seemed to have inferior PFS, independent central review did not confirm this finding.''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
@@ Line 1,419: / Line 1,604: @@
 ====Supportive medications====
 *Some protocols: "Hyperhydration" for [[Cisplatin (Platinol)]]
 '''21-day cycles, varied duration (see below)'''
 ====Subsequent treatment====
 *AVAGAST & AVATAR: after 6 cycles, [[#Capecitabine_monotherapy_2|capecitabine maintenance]]
 *Kim et al. 2014: after 8 cycles, [[#Capecitabine_monotherapy_2|capecitabine maintenance]]
 ===References===
-# Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [http://annonc.oxfordjournals.org/content/20/4/666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19153121 PubMed] content property of [http://hemonc.org HemOnc.org]
-# '''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.2236 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21844504 PubMed]
+#Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [http://annonc.oxfordjournals.org/content/20/4/666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19153121 PubMed] content property of [http://hemonc.org HemOnc.org]
-# '''EXPAND:''' Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23594786 PubMed]
+#'''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.2236 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21844504 PubMed]
-# '''AVATAR:''' Shen L, Li J, Xu J, Pan H, Dai G, Qin S, Wang L, Wang J, Yang Z, Shu Y, Xu R, Chen L, Liu Y, Yu S, Bu L, Piao Y. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015 Jan;18(1):168-76. Epub 2014 Feb 21. [https://link.springer.com/article/10.1007%2Fs10120-014-0351-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544634/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24557418 PubMed]
+#'''EXPAND:''' Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23594786 PubMed]
-# '''SMC 2008-12-019:''' Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. [https://www.ejcancer.com/article/S0959-8049(14)00884-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25218337 PubMed]
+#'''AVATAR:''' Shen L, Li J, Xu J, Pan H, Dai G, Qin S, Wang L, Wang J, Yang Z, Shu Y, Xu R, Chen L, Liu Y, Yu S, Bu L, Piao Y. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015 Jan;18(1):168-76. Epub 2014 Feb 21. [https://link.springer.com/article/10.1007%2Fs10120-014-0351-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544634/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24557418 PubMed]
-# '''PAC-C:''' Lu Z, Zhang X, Liu W, Liu T, Hu B, Li W, Fan Q, Xu J, Xu N, Bai Y, Pan Y, Xu Q, Bai W, Xia L, Gao Y, Wang W, Shu Y, Shen L. A multicenter, randomized trial comparing efficacy and safety of paclitaxel/capecitabine and cisplatin/capecitabine in advanced gastric cancer. Gastric Cancer. 2018 Sep;21(5):782-791. Epub 2018 Feb 27. [https://link.springer.com/article/10.1007%2Fs10120-018-0809-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097104/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29488121 PubMed]
+#'''SMC 2008-12-019:''' Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. [https://www.ejcancer.com/article/S0959-8049(14)00884-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25218337 PubMed]
-# '''RAINFALL:''' Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA; RAINFALL Study Group. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):420-435. Epub 2019 Feb 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30791-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30718072 PubMed]
+#'''PAC-C:''' Lu Z, Zhang X, Liu W, Liu T, Hu B, Li W, Fan Q, Xu J, Xu N, Bai Y, Pan Y, Xu Q, Bai W, Xia L, Gao Y, Wang W, Shu Y, Shen L. A multicenter, randomized trial comparing efficacy and safety of paclitaxel/capecitabine and cisplatin/capecitabine in advanced gastric cancer. Gastric Cancer. 2018 Sep;21(5):782-791. Epub 2018 Feb 27. [https://link.springer.com/article/10.1007%2Fs10120-018-0809-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097104/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29488121 PubMed]
+#'''RAINFALL:''' Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA; RAINFALL Study Group. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):420-435. Epub 2019 Feb 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30791-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30718072 PubMed]
 ==CX & Trastuzumab {{#subobject:7cbb79|Regimen=1}}==
@@ Line 1,458: / Line 1,646: @@
 ''Patients: 79% gastric, 21% GE junction, and all patients had an ECOG of 2''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 *[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 14
@@ Line 1,466: / Line 1,655: @@
 '''21-day cycle for up to 6 cycles'''
 ====Subsequent treatment====
 *Trastuzumab maintenance
@@ Line 1,490: / Line 1,680: @@
 ''ToGA patients: 81% gastric, 19% GE junction. 10% of patients with ECOG of 2.''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
@@ Line 1,499: / Line 1,690: @@
 ===References===
-# '''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
-# '''HELOISE:''' Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.[https://ascopubs.org/doi/full/10.1200/JCO.2016.71.6852 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28574779 PubMed]
+#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
-# '''JACOB:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30481-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30217672 PubMed]
+#'''HELOISE:''' Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.[https://ascopubs.org/doi/full/10.1200/JCO.2016.71.6852 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28574779 PubMed]
+#'''JACOB:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30481-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30217672 PubMed]
 ==DCF {{#subobject:efbdc5|Regimen=1}}==
@@ Line 1,536: / Line 1,728: @@
 ''Van Cutsem et al Patients: 100% adenocarcinoma histology (22% gastroesophageal junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS score of 70.''
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
@@ Line 1,541: / Line 1,734: @@
 ====Supportive medications====
 *(varied depending on reference):
 *[[Dexamethasone (Decadron)]] 8 mg PO once the night before chemotherapy, then 8 mg PO once on day 1; 1 hour prior to chemotherapy, then 8 mg PO twice per day until day 2 (total dose per cycle: 48 mg)
@@ Line 1,557: / Line 1,751: @@
 |-
 | rowspan="2" |[http://jco.ascopubs.org/content/25/22/3217.long Roth et al. 2007]
-| style="background-color:#1a9851" rowspan="2" |Randomized Phase II (E)
+| rowspan="2" style="background-color:#1a9851" |Randomized Phase II (E)
 |1. [[#ECF_3|ECF]]
 | style="background-color:#d3d3d3" |Not reported
@@ Line 1,567: / Line 1,761: @@
 ''Note: the protocol was amended to change the original dose of ''docetaxel from'' 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
@@ Line 1,572: / Line 1,767: @@
 ====Supportive medications====
 *3 liters per day "hyperhydration"
 *[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO twice per day for 4 days after [[Docetaxel (Taxotere)]]
@@ Line 1,580: / Line 1,776: @@
 ===References===
-# '''V-325:''' Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [http://jco.ascopubs.org/content/23/24/5660.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16110025 PubMed]
-# '''TAX 325:''' Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [http://jco.ascopubs.org/content/24/31/4991.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17075117 PubMed]
+#'''V-325:''' Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [http://jco.ascopubs.org/content/23/24/5660.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16110025 PubMed]
-# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
+#'''TAX 325:''' Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [http://jco.ascopubs.org/content/24/31/4991.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17075117 PubMed]
+#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
 ==mDCF {{#subobject:70e20f|Regimen=1}}==
@@ Line 1,603: / Line 1,800: @@
 ''Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.''
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 3
@@ Line 1,609: / Line 1,807: @@
 ====Supportive medications====
 *"Standard premedication and delayed emesis regimens"
@@ Line 1,615: / Line 1,814: @@
 ===Variant #2, 60/60/3000 {{#subobject:323b13|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://meetinglibrary.asco.org/content/1882-72 Ozal et al. 2010]
@@ Line 1,632: / Line 1,831: @@
 |}
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,640: / Line 1,840: @@
 '''21-day cycles'''
 ===References===
-# '''Abstract:''' G. Ozal, M. Dogan, H. Akbulut, B. Yalcin, G. Utkan, Y. Urun, F. Icli. The safety and efficacy of modified-dose docetaxel, cisplatin, and 5-fluorouracil (mDCF) combination in the front-line treatment of advanced gastric cancer. 2010 Gastrointestinal Cancers Symposium abstract 113. [http://meetinglibrary.asco.org/content/1882-72 link to abstract]
-# Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/7/868.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21189380 PubMed]
+#'''Abstract:''' G. Ozal, M. Dogan, H. Akbulut, B. Yalcin, G. Utkan, Y. Urun, F. Icli. The safety and efficacy of modified-dose docetaxel, cisplatin, and 5-fluorouracil (mDCF) combination in the front-line treatment of advanced gastric cancer. 2010 Gastrointestinal Cancers Symposium abstract 113. [http://meetinglibrary.asco.org/content/1882-72 link to abstract]
-# '''DOCET_L_02195:''' Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, Dai G, Xu J, Liu Y, Fan N, Shu Y, Ba Y, Ma D, Qin S, Zheng L, Chen W, Shen L. Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer. 2016 Jan;19(1):234-44. Epub 2015 Jan 21. [https://link.springer.com/article/10.1007%2Fs10120-015-0457-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688303/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25604851 PubMed]
+#Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/7/868.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21189380 PubMed]
+#'''DOCET_L_02195:''' Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, Dai G, Xu J, Liu Y, Fan N, Shu Y, Ba Y, Ma D, Qin S, Zheng L, Chen W, Shen L. Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer. 2016 Jan;19(1):234-44. Epub 2015 Jan 21. [https://link.springer.com/article/10.1007%2Fs10120-015-0457-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688303/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25604851 PubMed]
 ==mDCF & Bevacizumab {{#subobject:30ea9e|Regimen=1}}==
@@ Line 1,662: / Line 1,863: @@
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 3
@@ Line 1,667: / Line 1,869: @@
 *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 *[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
 ====Supportive medications====
 *"Standard premedication and delayed emesis regimens"
@@ Line 1,673: / Line 1,877: @@
 ===References===
-# Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/7/868.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21189380 PubMed]
+#Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/7/868.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21189380 PubMed]
 ==Docetaxel & S-1 {{#subobject:a22c2a|Regimen=1}}==
@@ Line 1,693: / Line 1,898: @@
 |}
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV once on day 1
 *[[Tegafur, gimeracil, oteracil (S-1)]] as follows:
@@ Line 1,702: / Line 1,908: @@
 ===References===
-# '''START:''' Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. [https://link.springer.com/article/10.1007%2Fs00432-013-1563-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24366758 PubMed]
+#'''START:''' Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. [https://link.springer.com/article/10.1007%2Fs00432-013-1563-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24366758 PubMed]
 ==ECF {{#subobject:6325cb|Regimen=1}}==
@@ Line 1,758: / Line 1,965: @@
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 4 hours once on day 1
@@ Line 1,763: / Line 1,971: @@
 ====Supportive medications====
 *(varied depending on reference):
 *3 liters per day "hyperhydration"
@@ Line 1,772: / Line 1,981: @@
 ===References===
-# Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. [http://annonc.oxfordjournals.org/content/5/7/609.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7993836 PubMed]
-# Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997 Jan;15(1):261-7. [https://ascopubs.org/doi/10.1200/JCO.1997.15.1.261 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8996151 PubMed]
+#Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. [http://annonc.oxfordjournals.org/content/5/7/609.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7993836 PubMed]
-## '''Update:''' Waters JS, Norman A, Cunningham D, Scarffe JH, Webb A, Harper P, Joffe JK, Mackean M, Mansi J, Leahy M, Hill A, Oates J, Rao S, Nicolson M, Hickish T. Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer. 1999 Apr;80(1-2):269-72. [https://www.nature.com/articles/6690350 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363002/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/10390007 PubMed]
+#Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997 Jan;15(1):261-7. [https://ascopubs.org/doi/10.1200/JCO.1997.15.1.261 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8996151 PubMed]
-# Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. [http://jco.ascopubs.org/content/20/8/1996.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11956258 PubMed]
+##'''Update:''' Waters JS, Norman A, Cunningham D, Scarffe JH, Webb A, Harper P, Joffe JK, Mackean M, Mansi J, Leahy M, Hill A, Oates J, Rao S, Nicolson M, Hickish T. Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer. 1999 Apr;80(1-2):269-72. [https://www.nature.com/articles/6690350 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363002/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/10390007 PubMed]
-# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
+#Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. [http://jco.ascopubs.org/content/20/8/1996.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11956258 PubMed]
-# '''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed]
+#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
+#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed]
 ==ECX {{#subobject:36cac7|Regimen=1}}==
@@ Line 1,803: / Line 2,013: @@
 ''Patients: ~80% gastric, 20% GE junction and 10% distal esophageal''
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,825: / Line 2,036: @@
 ====Chemotherapy====
 *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1, '''given first'''
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
@@ Line 1,832: / Line 2,044: @@
 ===References===
-# Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010 Dec;46(18):3200-4. Epub 2010 Aug 18. [https://www.ejcancer.com/article/S0959-8049(10)00731-8/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20727735 PubMed]
-# '''RILOMET-1:''' Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. Epub 2017 Sep 25. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30566-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28958504 PubMed]
+#Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010 Dec;46(18):3200-4. Epub 2010 Aug 18. [https://www.ejcancer.com/article/S0959-8049(10)00731-8/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20727735 PubMed]
+#'''RILOMET-1:''' Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. Epub 2017 Sep 25. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30566-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28958504 PubMed]
 ==Fluorouracil monotherapy {{#subobject:588907|Regimen=1}}==
@@ Line 1,872: / Line 2,085: @@
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
@@ Line 1,891: / Line 2,105: @@
 ''Note: this is an experimental arm that did not meet its primary endpoint; included here because it represents a de-escalation strategy.''
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 to 5
@@ Line 1,909: / Line 2,124: @@
 |}
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 12 mg/kg IV once per day on days 1 to 5
@@ Line 1,927: / Line 2,143: @@
 |}
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion
@@ Line 1,932: / Line 2,149: @@
 ===References===
-# Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, Pfeifle DM, Barlow JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma: fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985 Apr 12;253(14):2061-7. [https://jamanetwork.com/journals/jama/fullarticle/397816 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2579257 PubMed]
-# Kolarić K, Potrebica V, Stanovnik M. Controlled phase III clinical study of 4-epi-doxorubicin + 5-fluorouracil versus 5-fluorouracil alone in metastatic gastric and rectosigmoid cancer. Oncology. 1986;43(2):73-7. [https://www.karger.com/Article/Abstract/226337 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3513075 PubMed]
+#Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, Pfeifle DM, Barlow JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma: fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985 Apr 12;253(14):2061-7. [https://jamanetwork.com/journals/jama/fullarticle/397816 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2579257 PubMed]
-# Tebbutt NC, Norman A, Cunningham D, Iveson T, Seymour M, Hickish T, Harper P, Maisey N, Mochlinski K, Prior Y, Hill M. A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer. Ann Oncol. 2002 Oct;13(10):1568-75. [https://academic.oup.com/annonc/article/13/10/1568/167797 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12377644 PubMed]
+#Kolarić K, Potrebica V, Stanovnik M. Controlled phase III clinical study of 4-epi-doxorubicin + 5-fluorouracil versus 5-fluorouracil alone in metastatic gastric and rectosigmoid cancer. Oncology. 1986;43(2):73-7. [https://www.karger.com/Article/Abstract/226337 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3513075 PubMed]
-# '''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
+#Tebbutt NC, Norman A, Cunningham D, Iveson T, Seymour M, Hickish T, Harper P, Maisey N, Mochlinski K, Prior Y, Hill M. A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer. Ann Oncol. 2002 Oct;13(10):1568-75. [https://academic.oup.com/annonc/article/13/10/1568/167797 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12377644 PubMed]
-# '''JCOG 9912:''' Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70259-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19818685 PubMed]
+#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
-# '''JCOG 0106:''' Shirao K, Boku N, Yamada Y, Yamaguchi K, Doi T, Goto M, Nasu J, Denda T, Hamamoto Y, Takashima A, Fukuda H, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Randomized Phase III study of 5-fluorouracil continuous infusion vs sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106). Jpn J Clin Oncol. 2013 Oct;43(10):972-80. Epub 2013 Sep 7. [https://academic.oup.com/jjco/article/43/10/972/851849 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24014884 PubMed]
+#'''JCOG 9912:''' Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70259-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19818685 PubMed]
+#'''JCOG 0106:''' Shirao K, Boku N, Yamada Y, Yamaguchi K, Doi T, Goto M, Nasu J, Denda T, Hamamoto Y, Takashima A, Fukuda H, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Randomized Phase III study of 5-fluorouracil continuous infusion vs sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106). Jpn J Clin Oncol. 2013 Oct;43(10):972-80. Epub 2013 Sep 7. [https://academic.oup.com/jjco/article/43/10/972/851849 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24014884 PubMed]
 ==Fluorouracil, Folinic acid, Mitomycin {{#subobject:a4ca9d|Regimen=1}}==
@@ Line 1,954: / Line 2,172: @@
 |}
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours once per day on days 1, 8, 15, 22, 29, 36
 *[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
@@ Line 1,961: / Line 2,180: @@
 ===References===
-# Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12119460 PubMed]
+#Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12119460 PubMed]
 ==Irinotecan monotherapy {{#subobject:41e063|Regimen=1}}==
@@ Line 1,983: / Line 2,203: @@
 ''Regimen showed a 14% response rate and 53% disease control rate.''
 ====Chemotherapy====
 *[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22
@@ Line 1,988: / Line 2,209: @@
 ===References===
-# Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007%2Fs10620-005-3038-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16416165 PubMed]
+#Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007%2Fs10620-005-3038-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16416165 PubMed]
 ==OLF {{#subobject:98b4fa|Regimen=1}}==
@@ Line 2,013: / Line 2,235: @@
 ====Chemotherapy====
 *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
 *[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
@@ Line 2,018: / Line 2,241: @@
 ====Supportive medications====
 *Antiemetic medications per "local protocols"
@@ Line 2,023: / Line 2,247: @@
 ===References===
-# Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [http://jco.ascopubs.org/content/26/9/1435.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18349393 PubMed]
+#Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [http://jco.ascopubs.org/content/26/9/1435.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18349393 PubMed]
 ==Paclitaxel & S-1 {{#subobject:a88c2a|Regimen=1}}==
@@ Line 2,043: / Line 2,268: @@
 |}
 ''Note: Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details''
-==== Chemotherapy ====
+====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 and 8
 *[[Tegafur, gimeracil, oteracil (S-1)]] as follows:
-** 40 to 60 mg twice per day, depending on body surface area, as follows:
+**40 to 60 mg twice per day, depending on body surface area, as follows:
-*** if less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
+***if less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
-*** if 1.25 to less than 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
+***if 1.25 to less than 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
-*** if more than 1.5 m<sup>2</sup>: 60 mg PO twice per day on days 1 to 14
+***if more than 1.5 m<sup>2</sup>: 60 mg PO twice per day on days 1 to 14
 *[[Paclitaxel (Taxol)]] 20 mg/m<sup>2</sup> IP once per day over 1 hour on days 1 and 8
 ====Supportive medications====
-* 500 mL of normal saline was given prior to intraperitoneal [[Paclitaxel (Taxol)]]
+*500 mL of normal saline was given prior to intraperitoneal [[Paclitaxel (Taxol)]]
 '''35-day cycles'''
 ===References===
-# '''PHOENIX-GC:''' Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. [https://ascopubs.org/doi/full/10.1200/JCO.2018.77.8613 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29746229 PubMed]
+#'''PHOENIX-GC:''' Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. [https://ascopubs.org/doi/full/10.1200/JCO.2018.77.8613 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29746229 PubMed]
 ==S-1 monotherapy {{#subobject:a12a2a|Regimen=1}}==
@@ Line 2,082: / Line 2,310: @@
 |}
 ====Chemotherapy====
 *[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 28
@@ Line 2,116: / Line 2,345: @@
 ''Note: there is another trial named START in NSCLC.''
 ====Chemotherapy====
 *[[Tegafur, gimeracil, oteracil (S-1)]] as follows:
 **BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
@@ Line 2,123: / Line 2,353: @@
 '''42-day cycles'''
 ===References===
-# '''SPIRITS:''' Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70035-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18282805 PubMed]
-# '''JCOG 9912:''' Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70259-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19818685 PubMed]
+#'''SPIRITS:''' Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70035-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18282805 PubMed]
-# '''TOP-002:''' Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, Imamoto H, Esaki T, Furukawa H, Hamada C, Sakata Y. Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002). Gastric Cancer. 2011 Mar;14(1):72-80. Epub 2011 Feb 23. [https://link.springer.com/article/10.1007%2Fs10120-011-0009-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056989/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21340666 PubMed]
+#'''JCOG 9912:''' Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70259-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19818685 PubMed]
-# '''START:''' Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. [https://link.springer.com/article/10.1007%2Fs00432-013-1563-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24366758 PubMed]
+#'''TOP-002:''' Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, Imamoto H, Esaki T, Furukawa H, Hamada C, Sakata Y. Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002). Gastric Cancer. 2011 Mar;14(1):72-80. Epub 2011 Feb 23. [https://link.springer.com/article/10.1007%2Fs10120-011-0009-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056989/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21340666 PubMed]
-# '''JFMC36-0701:''' Yoshino S, Nishikawa K, Morita S, Takahashi T, Sakata K, Nagao J, Nemoto H, Murakami N, Matsuda T, Hasegawa H, Shimizu R, Yoshikawa T, Osanai H, Imano M, Naitoh H, Tanaka A, Tajiri T, Gochi A, Suzuki M, Sakamoto J, Saji S, Oka M. Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur J Cancer. 2016 Sep;65:164-71. Epub 2016 Aug 5. [https://www.ejcancer.com/article/S0959-8049(16)32267-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27501505 PubMed]
+#'''START:''' Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. [https://link.springer.com/article/10.1007%2Fs00432-013-1563-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24366758 PubMed]
+#'''JFMC36-0701:''' Yoshino S, Nishikawa K, Morita S, Takahashi T, Sakata K, Nagao J, Nemoto H, Murakami N, Matsuda T, Hasegawa H, Shimizu R, Yoshikawa T, Osanai H, Imano M, Naitoh H, Tanaka A, Tajiri T, Gochi A, Suzuki M, Sakamoto J, Saji S, Oka M. Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur J Cancer. 2016 Sep;65:164-71. Epub 2016 Aug 5. [https://www.ejcancer.com/article/S0959-8049(16)32267-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27501505 PubMed]
 ==UFTM {{#subobject:96e8bf|Regimen=1}}==
@@ Line 2,155: / Line 2,386: @@
 ====Chemotherapy====
 *[[Tegafur and uracil (UFT)]] 187.5 mg/m<sup>2</sup> PO twice per day
 *[[Mitomycin (Mutamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,162: / Line 2,394: @@
 ===References===
-# '''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
+#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
 =Maintenance after first-line therapy=
@@ Line 2,186: / Line 2,419: @@
 ''Kim et al patients: 79% gastric, 5% GEJ, and 16% unknown. 2% of patients had an ECOG of 2.''
 ====Preceding treatment====
 *AVAGAST: [[#CX_2|CX]] x 6
 *Kim et al. 2014: [[#CX_2|CX]] x 8
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 '''21-day cycles'''
 ===References===
-# Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.2236 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21844504 PubMed]
-# Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. [https://www.ejcancer.com/article/S0959-8049(14)00884-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25218337 PubMed]
+#Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.2236 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21844504 PubMed]
+#Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. [https://www.ejcancer.com/article/S0959-8049(14)00884-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25218337 PubMed]
 =Metastatic or locally advanced disease, subsequent lines of therapy=
@@ Line 2,237: / Line 2,474: @@
 ===References===
-# Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [https://www.ejcancer.com/article/S0959-8049(11)00396-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21742485 PubMed]
-# Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
+#Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [https://www.ejcancer.com/article/S0959-8049(11)00396-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21742485 PubMed]
-# '''COUGAR-02:''' Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70549-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24332238 PubMed]
+#Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
-# '''GRANITE-1:''' Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, Sahmoud T, Shen L, Yeh KH, Chin K, Muro K, Kim YH, Ferry D, Tebbutt NC, Al-Batran SE, Smith H, Costantini C, Rizvi S, Lebwohl D, Van Cutsem E. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013 Nov 1;31(31):3935-43. Epub 2013 Sep 16. [https://ascopubs.org/doi/full/10.1200/JCO.2012.48.3552 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24043745 PubMed]
+#'''COUGAR-02:''' Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70549-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24332238 PubMed]
+#'''GRANITE-1:''' Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, Sahmoud T, Shen L, Yeh KH, Chin K, Muro K, Kim YH, Ferry D, Tebbutt NC, Al-Batran SE, Smith H, Costantini C, Rizvi S, Lebwohl D, Van Cutsem E. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013 Nov 1;31(31):3935-43. Epub 2013 Sep 16. [https://ascopubs.org/doi/full/10.1200/JCO.2012.48.3552 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24043745 PubMed]
+== Apatinib monotherapy ==
+{| class="wikitable"
+|[[Gastric cancer#top|back to top]]
+|}
+=== Regimen ===
+{| class="wikitable"
+!Study
+![[Levels of Evidence#Evidence|Evidence]]
+!Comparator
+![[Levels of Evidence#Efficacy|Efficacy]]
+|-
+|Kang et al. 2019 (ANGEL)
+|Randomized Phase III
+|[[Gastric cancer#Placebo|Placebo]]
+|Superior PFS
+|}
+''ANGEL included patients with GEJ malignancy''
+==== Chemotherapy ====
+* Apatinib (Rivoceranib) 700 mg daily on days 1-28
+'''28-day cycles'''
+=== References ===
+# '''Abstract:''' Kang Y, Kang WK, Di Bartolomeo M, Chau I, Yoon HH, Cascinu S, Ryu M, Kim JG, Lee K, Oh SC, Takashima A, Kryzhanivska A, Chao Y, Vladimirov V, Evesque L, Schenker M, McGinn A, Sankar N, Wyrwicz L, Boku N. Randomized Phase 3 ANGEL study of rivoceranib (apatinib) + best supportive care (BSC) vs placebo + BSC in patients with advanced/metastatic gastric cancer. 2019 European Society of Medical Oncology annual meeting. Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394
 ==Docetaxel monotherapy {{#subobject:4f3230|Regimen=1}}==
@@ Line 2,261: / Line 2,528: @@
 |}
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,279: / Line 2,547: @@
 |}
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,300: / Line 2,569: @@
 ''Patients: 68% gastric, 32% GEJ''
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycles'''
 ===References===
-# Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
-# '''COUGAR-02:''' Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70549-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24332238 PubMed]
+#Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
-# '''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30111-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28343975 PubMed]
+#'''COUGAR-02:''' Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70549-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24332238 PubMed]
+#'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30111-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28343975 PubMed]
 ==Fluorouracil, Folinic acid, Mitomycin {{#subobject:b4ca9d|Regimen=1}}==
@@ Line 2,323: / Line 2,594: @@
 |}
 ====Chemotherapy====
 *[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours once per day on days 1, 8, 15, 22, 29, 36
 *[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
@@ Line 2,330: / Line 2,602: @@
 ===References===
-# Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12119460 PubMed]
+#Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12119460 PubMed]
 ==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}==
@@ Line 2,353: / Line 2,626: @@
 ====Chemotherapy====
 *[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22
@@ Line 2,398: / Line 2,672: @@
 ====Chemotherapy====
 *[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,416: / Line 2,691: @@
 ====Chemotherapy====
 *[[Irinotecan (Camptosar)]] 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1
@@ Line 2,436: / Line 2,712: @@
 ====Chemotherapy====
 *[[Irinotecan (Camptosar)]] as follows:
 **Cycle 1: 250 mg/m<sup>2</sup> (maximum dose of 500 mg) IV over 30 minutes once on day 1
@@ Line 2,441: / Line 2,718: @@
 ====Supportive medications====
 *[[Atropine (Atropen)]] 0.25 mg SC once on day 1, given prior to [[Irinotecan (Camptosar)]]
 *[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]]
 *[[Dexamethasone (Decadron)]]
@@ Line 2,448: / Line 2,726: @@
 ===References===
-# Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007%2Fs10620-005-3038-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16416165 PubMed]
-# Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [https://www.ejcancer.com/article/S0959-8049(11)00396-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21742485 PubMed]
+#Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007%2Fs10620-005-3038-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16416165 PubMed]
-# Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
+#Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [https://www.ejcancer.com/article/S0959-8049(11)00396-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21742485 PubMed]
-# '''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [http://annonc.oxfordjournals.org/content/24/6/1567.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23406728 PubMed]
+#Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
-# '''WJOG 4007:''' Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. [https://ascopubs.org/doi/full/10.1200/JCO.2012.48.5805 link to original artile] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24190112 PubMed]
+#'''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [http://annonc.oxfordjournals.org/content/24/6/1567.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23406728 PubMed]
-# '''BIRIP:''' Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, Takeda Y, Moriwaki T, Amagai K, Sekikawa T, Sakuyama T, Kanda T, Sasaki T, Azuma M, Takahashi F, Takeuchi M, Koizumi W; Tokyo Cooperative Oncology Group, Tokyo, Japan. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014 May;50(8):1437-45. Epub 2014 Feb 20. [https://www.ejcancer.com/article/S0959-8049(14)00093-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24560487 PubMed]
+#'''WJOG 4007:''' Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. [https://ascopubs.org/doi/full/10.1200/JCO.2012.48.5805 link to original artile] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24190112 PubMed]
-# '''TRICS:''' Nishikawa K, Fujitani K, Inagaki H, Akamaru Y, Tokunaga S, Takagi M, Tamura S, Sugimoto N, Shigematsu T, Yoshikawa T, Ishiguro T, Nakamura M, Morita S, Miyashita Y, Tsuburaya A, Sakamoto J, Tsujinaka T. Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial. Eur J Cancer. 2015 May;51(7):808-16. Epub 2015 Mar 18. [https://www.ejcancer.com/article/S0959-8049(15)00209-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25797356 PubMed]
+#'''BIRIP:''' Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, Takeda Y, Moriwaki T, Amagai K, Sekikawa T, Sakuyama T, Kanda T, Sasaki T, Azuma M, Takahashi F, Takeuchi M, Koizumi W; Tokyo Cooperative Oncology Group, Tokyo, Japan. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014 May;50(8):1437-45. Epub 2014 Feb 20. [https://www.ejcancer.com/article/S0959-8049(14)00093-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24560487 PubMed]
-# '''JACCRO GC-05:''' Tanabe K, Fujii M, Nishikawa K, Kunisaki C, Tsuji A, Matsuhashi N, Takagane A, Ohno T, Kawase T, Kochi M, Yoshida K, Kakeji Y, Ichikawa W, Chin K, Terashima M, Takeuchi M, Nakajima T; JACCRO GC-05 study group. Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05). Ann Oncol. 2015 Sep;26(9):1916-22. Epub 2015 Jun 24. [https://academic.oup.com/annonc/article/26/9/1916/189421 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26109630 PubMed]
+#'''TRICS:''' Nishikawa K, Fujitani K, Inagaki H, Akamaru Y, Tokunaga S, Takagi M, Tamura S, Sugimoto N, Shigematsu T, Yoshikawa T, Ishiguro T, Nakamura M, Morita S, Miyashita Y, Tsuburaya A, Sakamoto J, Tsujinaka T. Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial. Eur J Cancer. 2015 May;51(7):808-16. Epub 2015 Mar 18. [https://www.ejcancer.com/article/S0959-8049(15)00209-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25797356 PubMed]
-# '''JAVELIN Gastric 300:''' Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. [https://academic.oup.com/annonc/article/29/10/2052/5058079 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30052729 PubMed]
+#'''JACCRO GC-05:''' Tanabe K, Fujii M, Nishikawa K, Kunisaki C, Tsuji A, Matsuhashi N, Takagane A, Ohno T, Kawase T, Kochi M, Yoshida K, Kakeji Y, Ichikawa W, Chin K, Terashima M, Takeuchi M, Nakajima T; JACCRO GC-05 study group. Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05). Ann Oncol. 2015 Sep;26(9):1916-22. Epub 2015 Jun 24. [https://academic.oup.com/annonc/article/26/9/1916/189421 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26109630 PubMed]
+#'''JAVELIN Gastric 300:''' Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. [https://academic.oup.com/annonc/article/29/10/2052/5058079 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30052729 PubMed]
 ==Irinotecan liposomal monotherapy {{#subobject:9a99c8|Regimen=1}}==
@@ Line 2,475: / Line 2,754: @@
 |}
 ====Chemotherapy====
 *[[Irinotecan liposome (Onivyde)]] 120 mg/m<sup>2</sup> IV over 90 minutes once on day 1
@@ Line 2,480: / Line 2,760: @@
 ===References===
-# '''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [https://annonc.oxfordjournals.org/content/24/6/1567.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23406728 PubMed]
+#'''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [https://annonc.oxfordjournals.org/content/24/6/1567.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23406728 PubMed]
 ==Nivolumab monotherapy {{#subobject:7011e1|Regimen=1}}==
@@ Line 2,508: / Line 2,789: @@
 ====Immunotherapy====
 *[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
@@ Line 2,513: / Line 2,795: @@
 ===References===
-# '''ATTRACTION-2:''' Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31827-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28993052 PubMed]
-## '''Subgroup analysis:''' Kato K, Satoh T, Muro K, Yoshikawa T, Tamura T, Hamamoto Y, Chin K, Minashi K, Tsuda M, Yamaguchi K, Machida N, Esaki T, Goto M, Komatsu Y, Nakajima TE, Sugimoto N, Yoshida K, Oki E, Nishina T, Tsuji A, Fujii H, Kunieda K, Saitoh S, Omuro Y, Azuma M, Iwamoto Y, Taku K, Fushida S, Chen LT, Kang YK, Boku N. A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2). Gastric Cancer. 2019 Mar;22(2):344-354. Epub 2018 Dec 1. [https://link.springer.com/article/10.1007%2Fs10120-018-0899-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394726/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30506519 PubMed]
+#'''ATTRACTION-2:''' Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31827-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28993052 PubMed]
-# '''CheckMate-032:''' Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, Ott PA, Peltola K, Jaeger D, Evans J, de Braud F, Chau I, Harbison CT, Dorange C, Tschaika M, Le DT. CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. J Clin Oncol. 2018 Oct 1;36(28):2836-2844. Epub 2018 Aug 15. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.6212 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161834/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30110194 PubMed]
+##'''Subgroup analysis:''' Kato K, Satoh T, Muro K, Yoshikawa T, Tamura T, Hamamoto Y, Chin K, Minashi K, Tsuda M, Yamaguchi K, Machida N, Esaki T, Goto M, Komatsu Y, Nakajima TE, Sugimoto N, Yoshida K, Oki E, Nishina T, Tsuji A, Fujii H, Kunieda K, Saitoh S, Omuro Y, Azuma M, Iwamoto Y, Taku K, Fushida S, Chen LT, Kang YK, Boku N. A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2). Gastric Cancer. 2019 Mar;22(2):344-354. Epub 2018 Dec 1. [https://link.springer.com/article/10.1007%2Fs10120-018-0899-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394726/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30506519 PubMed]
+#'''CheckMate-032:''' Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, Ott PA, Peltola K, Jaeger D, Evans J, de Braud F, Chau I, Harbison CT, Dorange C, Tschaika M, Le DT. CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. J Clin Oncol. 2018 Oct 1;36(28):2836-2844. Epub 2018 Aug 15. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.6212 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161834/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30110194 PubMed]
 ==Paclitaxel monotherapy {{#subobject:2dcad9|Regimen=1}}==
@@ Line 2,536: / Line 2,819: @@
 |}
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 70 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
@@ Line 2,562: / Line 2,846: @@
 ''Study included patients with GE junction malignancy (68% gastric, 32% GE junction)''
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
@@ Line 2,626: / Line 2,911: @@
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
@@ Line 2,644: / Line 2,930: @@
 |}
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,649: / Line 2,936: @@
 ===References===
-# Hironaka S, Zenda S, Boku N, Fukutomi A, Yoshino T, Onozawa Y. Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2006;9(1):14-8. [https://link.springer.com/article/10.1007%2Fs10120-005-0351-6 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16557431 PubMed]
-# '''CCOG0302:''' Kodera Y, Ito S, Mochizuki Y, Fujitake S, Koshikawa K, Kanyama Y, Matsui T, Kojima H, Takase T, Ohashi N, Fujiwara M, Sakamoto J, Akimasa N; Chubu Clinical Cancer Group. A phase II study of weekly paclitaxel as second-line chemotherapy for advanced gastric cancer (CCOG0302 study). Anticancer Res. 2007 Jul-Aug;27(4C):2667-71. [http://ar.iiarjournals.org/content/27/4C/2667.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17695430 PubMed]
+#Hironaka S, Zenda S, Boku N, Fukutomi A, Yoshino T, Onozawa Y. Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2006;9(1):14-8. [https://link.springer.com/article/10.1007%2Fs10120-005-0351-6 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16557431 PubMed]
-# '''WJOG 4007:''' Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. [https://ascopubs.org/doi/full/10.1200/JCO.2012.48.5805 link to original artile] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24190112 PubMed]
+#'''CCOG0302:''' Kodera Y, Ito S, Mochizuki Y, Fujitake S, Koshikawa K, Kanyama Y, Matsui T, Kojima H, Takase T, Ohashi N, Fujiwara M, Sakamoto J, Akimasa N; Chubu Clinical Cancer Group. A phase II study of weekly paclitaxel as second-line chemotherapy for advanced gastric cancer (CCOG0302 study). Anticancer Res. 2007 Jul-Aug;27(4C):2667-71. [http://ar.iiarjournals.org/content/27/4C/2667.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17695430 PubMed]
-# '''TyTAN:''' Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. [https://ascopubs.org/doi/full/10.1200/JCO.2013.53.6136 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24868024 PubMed]
+#'''WJOG 4007:''' Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. [https://ascopubs.org/doi/full/10.1200/JCO.2012.48.5805 link to original artile] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24190112 PubMed]
-# '''RAINBOW:''' Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2970420-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25240821 PubMed]
+#'''TyTAN:''' Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. [https://ascopubs.org/doi/full/10.1200/JCO.2013.53.6136 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24868024 PubMed]
-# '''ABSOLUTE:''' Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(16)30219-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28404157 PubMed]
+#'''RAINBOW:''' Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2970420-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25240821 PubMed]
-# '''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30111-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28343975 PubMed]
+#'''ABSOLUTE:''' Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(16)30219-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28404157 PubMed]
-# '''GOLD:''' Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. Epub 2017 Nov 2. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30682-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29103871 PubMed]
+#'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30111-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28343975 PubMed]
-# '''DREAM:''' Kang YK, Ryu MH, Park SH, Kim JG, Kim JW, Cho SH, Park YI, Park SR, Rha SY, Kang MJ, Cho JY, Kang SY, Roh SY, Ryoo BY, Nam BH, Jo YW, Yoon KE, Oh SC. Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus IV paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Ann Oncol. 2018 May 1;29(5):1220-1226. [https://academic.oup.com/annonc/article-abstract/29/5/1220/4846849 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29438463 PubMed]
+#'''GOLD:''' Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. Epub 2017 Nov 2. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30682-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29103871 PubMed]
-# '''KEYNOTE-061:''' Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31257-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29880231 PubMed]
+#'''DREAM:''' Kang YK, Ryu MH, Park SH, Kim JG, Kim JW, Cho SH, Park YI, Park SR, Rha SY, Kang MJ, Cho JY, Kang SY, Roh SY, Ryoo BY, Nam BH, Jo YW, Yoon KE, Oh SC. Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus IV paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Ann Oncol. 2018 May 1;29(5):1220-1226. [https://academic.oup.com/annonc/article-abstract/29/5/1220/4846849 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29438463 PubMed]
-# '''KCSG ST10-01:''' Lee KW, Maeng CH, Kim TY, Zang DY, Kim YH, Hwang IG, Oh SC, Chung JS, Song HS, Kim JW, Jeong SJ, Cho JY. A phase III study to compare the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer who failed in first-line therapy (KCSG ST10-01). Oncologist. 2019 Jan;24(1):18-e24. Epub 2018 Aug 20. [http://theoncologist.alphamedpress.org/content/24/1/18.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324622/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30126861 PubMed]
+#'''KEYNOTE-061:''' Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31257-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29880231 PubMed]
-# '''JAVELIN Gastric 300:''' Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. [https://academic.oup.com/annonc/article/29/10/2052/5058079 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30052729 PubMed]
+#'''KCSG ST10-01:''' Lee KW, Maeng CH, Kim TY, Zang DY, Kim YH, Hwang IG, Oh SC, Chung JS, Song HS, Kim JW, Jeong SJ, Cho JY. A phase III study to compare the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer who failed in first-line therapy (KCSG ST10-01). Oncologist. 2019 Jan;24(1):18-e24. Epub 2018 Aug 20. [http://theoncologist.alphamedpress.org/content/24/1/18.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324622/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30126861 PubMed]
+#'''JAVELIN Gastric 300:''' Bang YJ, Ruiz EY, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. [https://academic.oup.com/annonc/article/29/10/2052/5058079 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30052729 PubMed]
 ==nab-Paclitaxel monotherapy {{#subobject:8f6227|Regimen=1}}==
@@ Line 2,684: / Line 2,972: @@
 |}
 ====Chemotherapy====
 *[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
@@ Line 2,689: / Line 2,978: @@
 ===References===
-# '''ABSOLUTE:''' Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(16)30219-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28404157 PubMed]
+#'''ABSOLUTE:''' Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(16)30219-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28404157 PubMed]
 ==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}==
@@ Line 2,722: / Line 3,012: @@
 ====Chemotherapy====
 *[[Ramucirumab (Cyramza)]] 8 mg/kg IV over 60 minutes once per day on days 1 & 15, '''given first'''
 *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, '''given second'''
@@ Line 2,728: / Line 3,019: @@
 ===References===
-# '''RAINBOW:''' Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2970420-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25240821 PubMed]
+#'''RAINBOW:''' Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2970420-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25240821 PubMed]
 ==Pembrolizumab monotherapy {{#subobject:88c665|Regimen=1}}==
@@ Line 2,755: / Line 3,047: @@
 |}
 ''Both studies included patients with GE junction malignancy:''
-* ''KEYNOTE-059: 48.3% gastric, 51.4% GE junction and 57.1% of patients had a PD-L1 CPS score of at least 1''
-* ''KEYNOTE-061: 68.8% gastric, 31.2% GE junction and 66% of all patients receiving pembrolizumab had a PD-L1 CPS score of at least 1''
+*''KEYNOTE-059: 48.3% gastric, 51.4% GE junction and 57.1% of patients had a PD-L1 CPS score of at least 1''
+*''KEYNOTE-061: 68.8% gastric, 31.2% GE junction and 66% of all patients receiving pembrolizumab had a PD-L1 CPS score of at least 1''
 ====Immunotherapy====
 *[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
@@ Line 2,766: / Line 3,060: @@
 ===References===
 <!-- # '''Abstract:''' Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, ...Weijing Sun, Shadia Ibrahim Jalal, Manish A. Shah, Jean-Philippe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A. Wainberg, Daniel V.T. Catenacci, Yung-Jue Bang, Jiangdian Wang, Minori Koshiji, Rita P. Dalal, Harry H. Yoon (2017). KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 4003-4003. [https://ascopubs.org/doi/full/10.1200/JCO.2017.35.15_suppl.4003 link to abstract] -->
-# '''KEYNOTE-059:''' Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018 May 10;4(5):e180013. Epub 2018 May 10. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2675013 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885175/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29543932 PubMed]
-# '''KEYNOTE-061:''' Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31257-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29880231 PubMed]
+#'''KEYNOTE-059:''' Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018 May 10;4(5):e180013. Epub 2018 May 10. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2675013 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885175/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29543932 PubMed]
+#'''KEYNOTE-061:''' Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31257-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29880231 PubMed]
 ==Placebo==
@@ Line 2,803: / Line 3,098: @@
 |}
 ''All studies included patients with GE junction malignancy:''
-* ''REGARD: 75% gastric, 25% GE junction''
-* ''INTEGRATE: 62% stomach or other, 38% GE junction''
+*''REGARD: 75% gastric, 25% GE junction''
-* ''ATTRACTION-2: 82.6% gastric, 8.5% GE junction''
+*''INTEGRATE: 62% stomach or other, 38% GE junction''
+*''ATTRACTION-2: 82.6% gastric, 8.5% GE junction''
 ''Patients in '''REGARD''' previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."''
@@ Line 2,811: / Line 3,108: @@
 ===References===
-# '''REGARD:''' Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3.[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961719-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24094768 PubMed]
-# '''INTEGRATE:''' Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. [https://ascopubs.org/doi/full/10.1200/JCO.2015.65.1901 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019744/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27325864 PubMed]
+#'''REGARD:''' Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3.[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961719-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24094768 PubMed]
-# '''ATTRACTION-2:''' Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31827-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28993052 PubMed]
+#'''INTEGRATE:''' Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. [https://ascopubs.org/doi/full/10.1200/JCO.2015.65.1901 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019744/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27325864 PubMed]
-# '''TAGS:''' Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30739-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30355453 PubMed]
+#'''ATTRACTION-2:''' Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31827-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28993052 PubMed]
+#'''TAGS:''' Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30739-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30355453 PubMed]
 ==Ramucirumab monotherapy {{#subobject:425b15|Regimen=1}}==
@@ Line 2,846: / Line 3,144: @@
 ''Study includes patients with GE junction malignancy (75% gastric, 25% GE junction).''
 ====Chemotherapy====
 *[[Ramucirumab (Cyramza)]] 8 mg/kg IV over 60 minutes once on day 1
@@ Line 2,851: / Line 3,150: @@
 ===References===
-# '''REGARD:''' Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961719-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24094768 PubMed]
+#'''REGARD:''' Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961719-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24094768 PubMed]
 ==Regorafenib monotherapy {{#subobject:022ef0|Regimen=1}}==
@@ Line 2,874: / Line 3,174: @@
 ====Chemotherapy====
 *[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21
@@ Line 2,879: / Line 3,180: @@
 ===References===
-# '''INTEGRATE:''' Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. [https://ascopubs.org/doi/full/10.1200/JCO.2015.65.1901 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019744/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27325864 PubMed]
+#'''INTEGRATE:''' Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. [https://ascopubs.org/doi/full/10.1200/JCO.2015.65.1901 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019744/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27325864 PubMed]
 ==Trifluridine and tipiracil monotherapy {{#subobject:938bf3|Regimen=1}}==
@@ Line 2,900: / Line 3,202: @@
 |}
 ====Chemotherapy====
 *[[Trifluridine and tipiracil (Lonsurf)]] 35 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12
@@ Line 2,905: / Line 3,208: @@
 ===References===
-# '''TAGS:''' Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30739-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30355453 PubMed]
+#'''TAGS:''' Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30739-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30355453 PubMed]
 [[Category:Gastric cancer regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Gastrointestinal cancers]]

Difference between revisions of "Gastric cancer"

Revision as of 03:16, 8 November 2019

Guidelines

CAP/ASCP/ASCO

ESMO

ESMO/ESSO/ESTRO

NCCN

Neoadjuvant chemotherapy

Cisplatin & Fluorouracil

Regimen

Chemotherapy

Subsequent treatment

References

ECF

Regimen

Chemotherapy

Supportive medications

Subsequent treatment

References

ECX

Regimen

Chemotherapy

Subsequent treatment

References

EOF

Regimen

Chemotherapy

Subsequent treatment

References

EOX

Regimen

Chemotherapy

Subsequent treatment

References

FLOT

Regimen

Chemotherapy

Subsequent treatment

References

No neoadjuvant therapy

Regimen

Subsequent treatment

References

Adjuvant therapy

CapeOx

Regimen

Preceding treatment

Chemotherapy

References

Carboplatin & Docetaxel

Regimen

Preceding treatment

Chemotherapy

References

Cisplatin & Fluorouracil

Regimen

Preceding treatment

Chemotherapy

References

CX

Regimen

Preceding treatment

Chemotherapy

References

ECF

Regimen

Preceding treatment

Chemotherapy

Supportive medications

References

ECX

Regimen

Preceding treatment

Chemotherapy

References

EOF

Regimen

Preceding treatment

Chemotherapy

References

Variant #1, 2000 mg/m²/day

Variant #2, 2500 mg/m²/day