Difference between revisions of "Pancreatic cancer"

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''Inferior to gemcitabine. Here for historical reference purposes, only.''
 
''Inferior to gemcitabine. Here for historical reference purposes, only.''
  
−
==== Chemotherapy[edit | edit source] ====
+
==== Chemotherapy ====
 
* [[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once weekly
 
* [[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once weekly
  

Revision as of 21:51, 7 June 2018

Section editor
Nkv.jpg
 Neeta K. Venepalli, MD, MBA
Chicago, IL
49 regimens on this page
82 variants on this page


Guidelines

ASCO

ESMO

NCCN

Adjuvant therapy

Capecitabine & Gemcitabine

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GemCap: Gemcitabine & Capecitabine

Regimen

Study Evidence Comparator Efficacy
Neoptolemos et al. 2017 (ESPAC-4) Phase III Gemcitabine Seems to have superior OS

Treatment starts within 12 weeks of surgery.

Preceding treatment

  • Surgery

Chemotherapy

28-day cycle for 6 cycles

References

  1. ESPAC-4: Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11;389(10073):1011-1024. Epub 2017 Jan 25. link to original article contains protocol PubMed

Fluorouracil & Folinic acid

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Regimen

Study Evidence Comparator Efficacy
Neoptolemos et al. 2001 (ESPAC-1) Phase III 5-FU & RT
5-FU & RT, then 5-FU & Leucovorin 		Seems to have superior OS (*)
Observation Superior OS (*)
Neoptolemos et al. 2010 (ESPAC-3) Phase III Gemcitabine Seems not superior

Note: efficacy for ESPAC-1 is based on the 2004 update.

Preceding treatment

  • Surgery

Chemotherapy

28-day cycle for 6 cycles

References

  1. Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001 Nov 10;358(9293):1576-85. link to original article PubMed
    1. Update: Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18;350(12):1200-10. link to original article contains verified protocol PubMed
  2. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010 Sep 8;304(10):1073-81. link to original article contains verified protocol PubMed

Fluorouracil, then Fluorouracil & RT

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Neoptolemos et al. 2001 (ESPAC-1) Phase III 5-FU & Leucovorin
Observation 		Seems to have inferior OS (*)
5-FU & RT, then 5-FU & Leucovorin Not reported
Regine et al. 2008 Phase III Gemcitabine, then Fluorouracil & RT, then Gemcitabine Seems not superior

Note: efficacy for ESPAC-1 is based on the 2004 update.

Preceding treatment

  • Surgery

Chemotherapy, part 1

21-day course, followed in 1 to 2 weeks by:

Chemoradiotherapy

  • Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion throughout radiation therapy
  • Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, for a total dose of 50.4 Gy. The last 5.4 Gy of the 50.4 Gy is limited to the tumor bed.

6-week course, followed in 3 to 5 weeks by:

Chemotherapy, part 2

6-week cycle for 2 cycles

References

  1. Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001 Nov 10;358(9293):1576-85. link to original article PubMed
    1. Update: Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18;350(12):1200-10. link to original article contains verified protocol PubMed
  2. Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. link to original article contains verified protocol PubMed

Gemcitabine monotherapy

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Regimen

Study Evidence Comparator Efficacy
Oettle et al. 2007 (CONKO-001) Phase III Observation Seems to have superior OS
Neoptolemos et al. 2010 (ESPAC-3) Phase III Fluorouracil & Leucovorin Seems not superior
Uesaka et al. 2016 (JASPAC 01) Phase III (C) S-1 Inferior OS
Neoptolemos et al. 2017 (ESPAC-4) Phase III Capecitabine & Gemcitabine Seems to have inferior OS

Treatment starts day 10 to 42 after surgery or after wound is healed.

Note: efficacy for CONKO-001 is based on the 2013 update.

Preceding treatment

  • Surgery

Chemotherapy

28-day cycle for up to 6 cycles

References

  1. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007 Jan 17;297(3):267-77. link to original article contains verified protocol PubMed
    1. Update: Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013 Oct 9;310(14):1473-81. link to original article PubMed
  2. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010 Sep 8;304(10):1073-81. link to original article contains verified protocol PubMed
  3. Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y; JASPAC 01 Study Group. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016 Jul 16;388(10041):248-57. Epub 2016 Jun 2. link to original article contains verified protocol PubMed
  4. Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11;389(10073):1011-1024. Epub 2017 Jan 25. link to original article contains protocol PubMed

Gemcitabine, then Fluorouracil & RT, then Gemcitabine

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Regine et al. 2008 Phase III Fluorouracil & RT Seems not superior

Preceding treatment

  • Surgery

Chemotherapy, part 1

21-day course, followed in 1 to 2 weeks by:

Chemoradiotherapy

  • Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion throughout radiation therapy
  • Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, for a total dose of 50.4 Gy. The last 5.4 Gy of the 50.4 Gy is limited to the tumor bed.

6-week course, followed in 3 to 5 weeks by:

Chemotherapy, part 2

28-day cycle for 3 cycles

References

  1. Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. link to original article contains verified protocol PubMed

Observation

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Regimen

Study Evidence Comparator Efficacy
Neoptolemos et al. 2001 (ESPAC-1) Phase III (C) 5-FU & Leucovorin Inferior OS
5-FU & RT
5-FU & RT, then 5-FU & Leucovorin 		Seems to have superior OS
Oettle et al. 2007 (CONKO-001) Phase III (C) Gemcitabine Seems to have inferior OS

No active antineoplastic treatment. Efficacy for ESPAC-1 is based on the 2004 update and efficacy for CONKO-001 is based on 2013 update.

Preceding treatment

  • Surgery

References

  1. Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001 Nov 10;358(9293):1576-85. link to original article PubMed
    1. Update: Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18;350(12):1200-10. link to original article contains verified protocol PubMed
  2. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007 Jan 17;297(3):267-77. link to original article contains verified protocol PubMed
    1. Update: Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013 Oct 9;310(14):1473-81. link to original article PubMed

S-1 monotherapy

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Regimen

Study Evidence Comparator Efficacy
Uesaka et al. 2016 (JASPAC 01) Phase III (E) Gemcitabine Superior OS

Treatment starts day 10 to 42 after surgery or after wound is healed.

Preceding treatment

  • Surgery

Chemotherapy

  • Tegafur, gimeracil, oteracil (S-1) as follows:
    • BSA less than 1.25 m2: 40 mg PO BID on days 1 to 28
    • BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO BID on days 1 to 28
    • BSA 1.5 m2 or more: 60 mg PO BID on days 1 to 28

42-day cycle for up to 4 cycles

References

  1. Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y; JASPAC 01 Study Group. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016 Jul 16;388(10041):248-57. Epub 2016 Jun 2. link to original article contains verified protocol PubMed

Induction therapy for locally advanced disease, potentially resectable

Docetaxel, Gemcitabine, RT

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RT: Radiation Therapy

Regimen

Study Evidence
Pipas et al. 2005 Phase II

Chemotherapy

6-week course, followed immediately (day 43) by:

Chemoradiation

  • Gemcitabine (Gemzar) 50 mg/m2 IV over 30 minutes twice per week for 12 doses
    • Given Monday/Thursday or Tuesday/Friday. Infusion completed ½ to 2 hours prior to RT.
  • Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy to primary target volume. Then 5.4 Gy boost to secondary target volume of 1- to 1.5-cm margin on all sides, including proven nodal involvement. Total 50.4 Gy in 28 fractions.

Supportive medications

  • GI prophylaxis with a proton pump inhibitor during chemoradiotherapy

6-week course

References

  1. Pipas JM, Barth RJ Jr, Zaki B, Tsapakos MJ, Suriawinata AA, Bettmann MA, Cates JM, Ripple GH, Sutton JE, Gordon SR, McDonnell CE, Perez RP, Redfield N, Meyer LP, Marshall JF, Cole BF, Colacchio TA. Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. Ann Surg Oncol. 2005 Dec;12(12):995-1004. Epub 2005 Nov 1. link to original article contains verified protocol PubMed

Gemcitabine & RT

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RT: Radiation Therapy

Regimen 1

Study Evidence
Takahashi et al. 2013 Phase II

Chemoradiotherapy

  • Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
  • Concurrent radiation therapy, 2 Gy per fraction, 5 days per week, 25 fractions, total dose of 50 Gy over 5 weeks.

28-day cycle for 3 cycles (Radiation given over weeks 1-5 only)

Restaging is performed 8 weeks after radiation complete (2 weeks after chemotherapy complete). Resection immediately thereafter, if feasible.

Regimen 2

Study Evidence
Landry et al. 2010 Phase II

Chemoradiotherapy

  • Gemcitabine (Gemzar) 500 mg/m2 IV over 50 minutes once per week for 6 weeks
  • Concurrent radiation therapy, 180 cGy x 22 with 3 cm margin to GTV then 180 cGy x 6 with 2 cm margin to GTV, total 50.4 Gy over 6 weeks

Restaging after radiation complete. 4 to 6 week break, followed by surgery, followed by 4 to 8 week break. Then adjuvant chemotherapy:

Adjuvant chemotherapy

21-day cycle for 5 cycles

References

  1. Landry J, Catalano PJ, Staley C, Harris W, Hoffman J, Talamonti M, Xu N, Cooper H, Benson AB 3rd. Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol. 2010 Jun 1;101(7):587-92. link to original article contains verified protocol link to PMC article PubMed
  2. Takahashi H, Ohigashi H, Gotoh K, Marubashi S, Yamada T, Murata M, Ioka T, Uehara H, Yano M, Ishikawa O. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013 Dec;258(6):1040-50.link to original article contains verified protocol PubMed

Gemcitabine, Cetuximab, RT

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RT: Radiation Therapy

Regimen

Study Evidence
Pipas et al. 2012 Phase II

Chemoradiotherapy

  • Cetuximab (Erbitux) as follows:
    • 6 to 8 days prior radiation: 400 mg/m2 IV over 2 hours once
    • During radiation: 250 mg/m2 over 60 minutes once per week for 6 doses
  • Gemcitabine (Gemzar) 50 mg/m2 IV over 30 minutes twice per week for 12 doses
    • Given Monday/Thursday or Tuesday/Friday. Infusion completed ½ to 2 hours prior to RT.
  • Concurrent radiation therapy, delivered using IMRT. Gross tumor volume (GTV) was all known disease including imaging proven nodal disease. The primary planning target volume (PTV1) included the GTV with 2- to 3-cm margins in all directions as well as potential nodal involvement. Secondary planning target volume (PTV2) included the GTV with 1- to 1.5-cm margins on all sides including proven nodal involvement. Tertiary planning treatment volume (PTV3) included the area of the GTV adjacent to the vascular structures specifically the mesenteric and portal vessels with a 0.5-cm margin. The prescription dose delivered to PTV3 was 54 Gy in 28 fractions. Synchronously, PTV1 and PTV2 received 45 and 50.4 Gy, respectively. All fields were treated daily at five fractions per week.

Supportive medications

  • GI prophylaxis with a proton pump inhibitor during chemoradiotherapy

6-week course

One month following therapy, patients were restaged with CT scan of chest/abdomen/pelvis. Patients deemed to be candidates for surgical resection were offered laparotomy ∼6 to 10 weeks after completion of neoadjuvant therapy.

References

  1. Pipas JM, Zaki BI, McGowan MM, Tsapakos MJ, Ripple GH, Suriawinata AA, Tsongalis GJ, Colacchio TA, Gordon SR, Sutton JE, Srivastava A, Smith KD, Gardner TB, Korc M, Davis TH, Preis M, Tarczewski SM, Mackenzie TA, Barth RJ Jr. Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. Ann Oncol. 2012 Nov;23(11):2820-7. Epub 2012 May 9. link to original article contains verified protocol link to PMC article PubMed

mFOLFIRINOX, Gemcitabine, RT

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mFOLFIRINOX, Gemcitabine, RT: modified FOLinic acid, Fluorouracil, IRINotecan, OXaliplatin, Gemcitabine, Radiation Therapy

Variant #1

Study Evidence
Blazer et al. 2015 Retrospective

Chemotherapy, mFOLFIRINOX portion

Supportive medications

14-day cycle for 4 to 8 cycles

Followed by complete restaging. If tumor localized but still not resectable, chemoradiotherapy was administered:

Chemoradiotherapy

  • Gemcitabine (Gemzar) 1000 mg/m2/week concurrent with radiation
  • Radiation was 36 Gy in 15 daily fractions

Variant #2

Study Evidence
Hosein et al. 2012 Retrospective

Chemotherapy, mFOLFIRINOX portion

14-day cycles. Protocol followed "per ACCORD-11 trial." Filgrastim was given at the discretion of the treating physician.

Treatment stopped at maximum response or tolerability. Resectable patients by imaging criteria were offered surgery, followed by postoperative chemoradiotherapy. Unresectable patients were offered chemoradiotherapy, followed by surgery (if they became resectable):

Chemoradiotherapy

References

  1. Retrospective: Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, Narayanan G, Ribeiro A, Portelance L, Merchan JR, Levi JU, Rocha-Lima CM. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012 May 29;12:199. link to original article link to PMC article PubMed
  2. Retrospective: Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, Wuthrick E, Williams TM, Reardon J, Christopher Ellison E, Bloomston M, Bekaii-Saab T. Neoadjuvant Modified (m) FOLFIRINOX for Locally Advanced Unresectable (LAPC) and Borderline Resectable (BRPC) Adenocarcinoma of the Pancreas. Ann Surg Oncol. 2015 Apr;22(4):1153-9. link to original article link to PMC article PubMed

Induction therapy for locally advanced disease, unresectable

Capecitabine monotherapy

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Regimen

Study Evidence
Cartwright et al. 2002 Phase II

Chemotherapy

21-day cycle for up to 1 year

References

  1. Cartwright TH, Cohn A, Varkey JA, Chen YM, Szatrowski TP, Cox JV, Schulz JJ. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol. 2002 Jan 1;20(1):160-4. link to original article contains verified protocol PubMed

Erlotinib & Gemcitabine

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Variant #1, Gem 3 out of 4 weeks x 4

Study Evidence Comparator Efficacy
Hammel et al. 2016 (GERCOR LAP07) Phase III See link See link

Chemotherapy

28-day cycle for 4 cycles

Subsequent treatment

  • Patients without progression: Erlotinib & Gemcitabine x 2 more cycles (6 total) versus Capecitabine, Erlotinib, RT

Variant #2, Gem 3 out of 4 weeks x 6

Study Evidence Comparator Efficacy
Hammel et al. 2016 (GERCOR LAP07) Phase III See link See link

Note: it is not clear from the protocol whether erlotinib is continued beyond the end of chemotherapy.

Chemotherapy

28-day cycle for 6 cycles

Variant #3, gemcitabine lead-in, erlotinib 100 mg/d

FDA-recommended dose
Study Evidence Comparator Efficacy
Moore et al. 2007 (NCIC CTG PA.3) Phase III (E) Gemcitabine Seems to have superior OS

Chemotherapy

  • Erlotinib (Tarceva) 100 mg PO once per day
  • Gemcitabine (Gemzar) as follows:
    • Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
    • Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15

One 8-week cycle, then 28-day cycles

Variant #4, gemcitabine lead-in, erlotinib 150 mg/d

Study Evidence Comparator Efficacy
Moore et al. 2007 (NCIC CTG PA.3) Phase III (E) Gemcitabine Not reported

Note: due to low accrual, the efficacy of this arm could not be determined.

Chemotherapy

  • Erlotinib (Tarceva) 150 mg PO once per day
  • Gemcitabine (Gemzar) as follows:
    • Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
    • Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15

One 8-week cycle, then 28-day cycles

References

  1. NCIC CTG PA.3: Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23. link to original article contains verified protocol PubMed
  2. GERCOR LAP07: Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. link to original article contains verified protocol PubMed

Fluorouracil & RT

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Herman et al. 2013 Phase III (C) Fluorouracil & RT with TNFerade Seems not superior

Chemoradiotherapy

  • Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion once per day on radiation days (total dose per week: 1000 mg/m2)
  • Concurrent radiation therapy, 50.4 Gy total: 1.80 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy, followed by 1.80 Gy x 3 fractions boost to the tumor bed.

One course

Subsequent treatment until progression or toxicity (starting four weeks after chemoradiotherapy)

  • Gemcitabine or Erlotinib & Gemcitabine maintenance

References

  1. Herman JM, Wild AT, Wang H, Tran PT, Chang KJ, Taylor GE, Donehower RC, Pawlik TM, Ziegler MA, Cai H, Savage DT, Canto MI, Klapman J, Reid T, Shah RJ, Hoffe SE, Rosemurgy A, Wolfgang CL, Laheru DA. Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: final results. J Clin Oncol. 2013 Mar 1;31(7):886-94. Epub 2013 Jan 22. link to original article contains verified protocol link to PMC article PubMed

Gemcitabine monotherapy

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Variant #1, 3 out of 4 weeks x 4

Study Evidence Comparator Efficacy
Hammel et al. 2016 (GERCOR LAP07) Phase III See link See link

Chemotherapy

28-day cycle for 4 cycles

Subsequent treatment

  • Patients without progression: Gemcitabine x 2 more cycles (6 total) versus Capecitabine & RT

Variant #2, 3 out of 4 weeks x 6

Study Evidence Comparator Efficacy
Hammel et al. 2016 (GERCOR LAP07) Phase III See link See link

Chemotherapy

28-day cycle for 6 cycles

Variant #3, 8-week lead-in

Study Evidence Comparator Efficacy
Louvet et al. 2005 Phase III GemOx Seems to have inferior PFS
Loehrer et al. 2011 Phase III Gemcitabine & RT Seems to have inferior OS

Chemotherapy

  • Gemcitabine (Gemzar) as follows:
    • First 8 weeks: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
    • Subsequent 4-week cycles: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15

Continued for at least 3 months

Per Louvet et al. 2005, subsequent chemoradiotherapy (45 Gy in 25 fractions for 5 weeks, associated with a daily FU 250 mg/m2 continuous infusion, and a boost of 10 Gy in 8 fractions restricted to the initial tumor volume) was recommended but not mandated.

References

  1. Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article contains verified protocol PubMed
  2. Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. Epub 2011 Oct 3. link to original article contains verified protocol link to PMC article PubMed
  3. Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. link to original article contains verified protocol PubMed

Gemcitabine & RT

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RT: Radiation Therapy

Variant #1 (600 mg/m2)

Study Evidence Comparator Efficacy
Cardenes et al. 2011 Phase II
Loehrer et al. 2011 Phase III Gemcitabine Seems to have superior OS

Chemoradiotherapy

  • Gemcitabine (Gemzar) 600 mg/m2 IV over 30 to 60 minutes once per week during radiation
  • Concurrent radiation therapy, 1.8 Gy per fraction, 5 days per week, 28 fractions, total dose of 50.4 Gy over 5.5 weeks.

One course, followed in 4 weeks by:

Maintenance chemotherapy

28-day cycle for 5 cycles or until disease progression

Variant #2 (400 mg/m2)

Study Evidence
Epelbaum et al. 2002 Phase II

Chemotherapy

Radiation planning during this phase, followed by:

Chemoradiotherapy

  • Gemcitabine (Gemzar) 400 mg/m2 IV over 30 minutes once per week (days 1, 8, 15)
  • Concurrent radiation therapy, 5 days per week, 28 fractions, total dose of 50.4 Gy over 5.5 weeks

28 day cycle for 2 cycles, followed by:

Maintenance chemotherapy

28-day cycles until disease progression

References

  1. Epelbaum R, Rosenblatt E, Nasrallah S, Faraggi D, Gaitini D, Mizrahi S, Kuten A. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol. 2002 Nov;81(3):138-43. link to original article contains verified protocol PubMed
  2. Cardenes HR, Moore AM, Johnson CS, Yu M, Helft P, Chiorean EG, Vinson J, Howard TJ, Stephens AW, Tai DF, Loehrer PJ Sr. A phase II study of gemcitabine in combination with radiation therapy in patients with localized, unresectable, pancreatic cancer: a Hoosier Oncology Group study. Am J Clin Oncol. 2011 Oct;34(5):460-5.link to original article PubMed
  3. Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. link to original article contains verified protocol link to PMC article PubMed

GemOx

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GemOx: Gemcitabine, Oxaliplatin

Regimen

Study Evidence Comparator Efficacy
Louvet et al. 2005 Phase III Gemcitabine Seems to have superior PFS

Chemotherapy

14-day cycle for at least 3 months

Subsequent chemoradiotherapy (45 Gy in 25 fractions for 5 weeks, associated with a daily FU 250 mg/m2 continuous infusion, and a boost of 10 Gy in 8 fractions restricted to the initial tumor volume) was recommended but not mandated.

References

  1. Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article contains verified protocol PubMed

Metastatic disease, first-line

Capecitabine monotherapy

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Regimen

Study Evidence
Cartwright et al. 2002 Phase II

Chemotherapy

21-day cycle for up to 1 year

References

  1. Cartwright TH, Cohn A, Varkey JA, Chen YM, Szatrowski TP, Cox JV, Schulz JJ. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol. 2002 Jan 1;20(1):160-4. link to original article contains verified protocol PubMed

Capecitabine & Gemcitabine

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GemCap/GEM-CAP: Gemcitabine & Capecitabine

Variant #1

Study Evidence Comparator Efficacy
Lee et al. 2017 Phase III Gemcitabine Might have superior OS

Note: this is essentially identical to the maintenance phase of Cunningham et al. 2009, below.

Chemotherapy

28-day cycles

Variant #2

Study Evidence Comparator Efficacy
Cunningham et al. 2009 Phase III Gemcitabine Superior PFS

Initial chemotherapy

8-week course, followed by:

Maintenance chemotherapy

28-day cycles

Variant #3

Study Evidence Comparator Efficacy
Herrmann et al. 2007 (SAKK 44/00-CECOG/PAN.1.3.001) Phase III Gemcitabine Seems not superior

Chemotherapy

21-day cycle for up to 24 weeks

References

  1. Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W; Swiss Group for Clinical Cancer Research; Central European Cooperative Oncology Group. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 2007 Jun 1;25(16):2212-7. link to original article contains verified protocol PubMed
    1. CBR/QoL analysis: Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R; Central European Cooperative Oncology Group. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol. 2008 Aug 1;26(22):3695-701. link to original article contains verified protocol PubMed
  2. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20;27(33):5513-8. Epub 2009 Oct 26. link to original article contains verified protocol PubMed
  3. Lee HS, Chung MJ, Park JY, Bang S, Park SW, Kim HG, Noh MH, Lee SH, Kim YT, Kim HJ, Kim CD, Lee DK, Cho KB, Cho CM, Moon JH, Kim DU, Kang DH, Cheon YK, Choi HS, Kim TH, Kim JK, Moon J, Shin HJ, Song SY; Korean Society of Gastrointestinal Cancer. A randomized, multicenter, phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea. Medicine (Baltimore). 2017 Jan;96(1):e5702. contains verified protocol link to PMC article PubMed

Cisplatin & Gemcitabine

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Variant #1, weekly dosing

Study Evidence Comparator Efficacy
Colucci et al. 2010 (GIP-1) Phase III (E) Gemcitabine Seems not superior

Note that cisplatin is not given on day 22 of the first 8 weeks; otherwise, the schedule is identical to the schedule for gemcitabine.

Chemotherapy

  • Cisplatin (Platinol) as follows, given 60 minutes prior to gemcitabine:
    • First 8 weeks: 25 mg/m2 IV once per day on days 1, 8, 15, 29, 36, 43
    • Subsequent cycles: 25 mg/m2 IV once per day on days 1, 8, 15
  • Gemcitabine (Gemzar) as follows:
    • First 8 weeks: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
    • Subsequent cycles: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15

28-day cycles

Variant #2, bi-weekly dosing

Study Evidence Comparator Efficacy
Heinemann et al. 2006 Phase III (E) Gemcitabine Might have superior PFS

Chemotherapy

28-day cycles

Variant #3, Day 1, 8 dosing

Study Evidence Comparator Efficacy
Cascinu et al. 2008 (GISCAD) Randomized Phase II (C) Cisplatin, Gemcitabine, Cetuximab Seems not superior

Chemotherapy

21-day cycles

References

  1. Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, Rost A, Neuhaus H, Haag C, Clemens M, Heinrich B, Vehling-Kaiser U, Fuchs M, Fleckenstein D, Gesierich W, Uthgenannt D, Einsele H, Holstege A, Hinke A, Schalhorn A, Wilkowski R. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 2006 Aug 20;24(24):3946-52. link to original article contains verified regimen PubMed
  2. Cascinu S, Berardi R, Labianca R, Siena S, Falcone A, Aitini E, Barni S, Di Costanzo F, Dapretto E, Tonini G, Pierantoni C, Artale S, Rota S, Floriani I, Scartozzi M, Zaniboni A; Italian Group for the Study of Digestive Tract Cancer (GISCAD). Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, phase II trial. Lancet Oncol. 2008 Jan;9(1):39-44. link to original article contains protocol PubMed
  3. Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F; Gruppo Oncologico Italia Meridionale (GOIM).; Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente (GISCAD).; Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC). Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010 Apr 1;28(10):1645-51. link to original article contains verified protocol PubMed

Erlotinib & Gemcitabine

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Variant #1, no gemcitabine lead-in

Study Evidence Comparator Efficacy
Kordes et al. 2015 Randomized Phase II (C) Erlotinib, Gemcitabine, Metformin Seems not superior

Chemotherapy

28-day cycles

Variant #2, gemcitabine lead-in, erlotinib 100 mg/d

FDA-recommended dose
Study Evidence Comparator Efficacy
Moore et al. 2007 (NCIC CTG PA.3) Phase III (E) Gemcitabine Seems to have superior OS

Chemotherapy

  • Erlotinib (Tarceva) 100 mg PO once per day
  • Gemcitabine (Gemzar) as follows:
    • Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
    • Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15

One 8-week cycle, then 28-day cycles

Variant #3, gemcitabine lead-in, erlotinib 150 mg/d

Study Evidence Comparator Efficacy
Moore et al. 2007 (NCIC CTG PA.3) Phase III (E) Gemcitabine Not reported

Note: due to low accrual, the efficacy of this arm could not be determined.

Chemotherapy

  • Erlotinib (Tarceva) 150 mg PO once per day
  • Gemcitabine (Gemzar) as follows:
    • Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
    • Cycle 2 onwards: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15

One 8-week cycle, then 28-day cycles

References

  1. NCIC CTG PA.3: Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23. link to original article contains verified protocol PubMed
  2. Kordes S, Pollak MN, Zwinderman AH, Mathôt RA, Weterman MJ, Beeker A, Punt CJ, Richel DJ, Wilmink JW. Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol. 2015 Jul;16(7):839-47. Epub 2015 Jun 8. link to original articlecontains protocol PubMed

Fluorouracil monotherapy

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Regimen

Study Evidence Comparator Efficacy
Burris et al. 1997 Phase III Gemcitabine Inferior OS

Inferior to gemcitabine. Here for historical reference purposes, only.

Chemotherapy

References

  1. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. link to original article contains verified protocol PubMed

FOLFIRINOX

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FOLFIRINOX: FOLinic acid, Fluorouracil, IRINotecan, OXaliplatin

Regimen

Study Evidence Comparator Efficacy Toxicity
Conroy et al. 2011 (PRODIGE 4/ACCORD 11) Phase III Gemcitabine Superior OS Superior QoL by EORTC QLQ-C30

Chemotherapy

  • Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given second
  • Fluorouracil (5-FU) 400 mg/m2 IV bolus, then 1200 mg/m2/day IV continuous 46-hour infusion on days 1 to 2; given last (total dose per cycle: 2400 mg/m2)
  • Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1; given third together with the last 90 minutes of leucovorin; that is, irinotecan starts 30 minutes after the start of leucovorin
  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first

14-day cycles

References

  1. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. link to original article contains verified protocol PubMed
    1. QoL analysis: Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Boige V, Bérille J, Conroy T. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol. 2013 Jan 1;31(1):23-9. Epub 2012 Dec 3. link to original article PubMed

Gemcitabine monotherapy

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Variant #1, 8-week lead-in

Study Evidence Comparator Efficacy
Burris et al. 1997 Phase III (E) 5-FU Superior OS
Louvet et al. 2005 Phase III (C) GemOx Seems to have inferior PFS
Reni et al. 2005 Phase III (C) PEFG Seems to have inferior PFS
Moore et al. 2007 Phase III (C) Erlotinib & Gemcitabine Seems to have inferior OS
Herrmann et al. 2007 (SAKK 44/00-CECOG/PAN.1.3.001) Phase III (C) GemCap Seems not superior
Poplin et al. 2009 (ECOG E6201) Phase III (C) GEM FDR Might have inferior OS
GEMOX Seems not superior
Cunningham et al. 2009 Phase III (C) GEM-CAP Inferior PFS
Colucci et al. 2010 (GIP-1) Phase III (C) Cisplatin & Gemcitabine Seems not superior
Philip et al. 2010 (SWOG S0205) Phase III (C) Gemcitabine & Cetuximab Seems not superior
Conroy et al. 2011 (PRODIGE 4/ACCORD 11) Phase III (C) FOLFIRINOX Inferior OS
Von Hoff et al. 2013 (MPACT) Phase III (C) Gemcitabine & nab-Paclitaxel Inferior OS
Middleton et al. 2017 (ViP) Randomized Phase II (C) Gemcitabine & Vandetanib Seems not superior

Chemotherapy

  • Gemcitabine (Gemzar) as follows:
    • First 8 weeks: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43
    • Subsequent cycles: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
      • In Burris et al. 1997, patients with grade 2 or lower toxicities could have had doses increased to 1250 mg/m2

28-day cycles

Variant #2, 4 week cycles

Study Evidence Comparator Efficacy
Heinemann et al. 2006 Phase III Cisplatin & Gemcitabine Might have inferior PFS
Kindler et al. 2011 Phase III Gemcitabine & Axitinib Seems not superior
Ueno et al. 2013 (GEST) Phase III (C) S-1 Non-inferior OS
Gemcitabine & S-1 Seems not superior
Fuchs et al. 2015 (GAMMA) Randomized Phase Ib/II Gemcitabine & Ganitumab Seems not superior
Catenacci et al. 2015 Randomized Phase Ib/II Gemcitabine & Vismodegib Seems not superior
Lee et al. 2017 Phase III GemCap Might have inferior OS

Chemotherapy

28-day cycles

Variant #3, 3 week cycles

Study Evidence Comparator Efficacy
Hong et al. 2013 Randomized Phase II Gemcitabine & Simvastatin Seems not superior

Chemotherapy

21-day cycles

Variant #4, fixed-dose rate (FDR)

Study Evidence Comparator Efficacy
Poplin et al. 2009 (ECOG E6201) Phase III Gemcitabine Might have superior OS
GEMOX Not reported

Chemotherapy

28-day cycles

References

  1. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. link to original article contains verified protocol PubMed
  2. Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article contains verified protocol PubMed
  3. Reni M, Cordio S, Milandri C, Passoni P, Bonetto E, Oliani C, Luppi G, Nicoletti R, Galli L, Bordonaro R, Passardi A, Zerbi A, Balzano G, Aldrighetti L, Staudacher C, Villa E, Di Carlo V. Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial. Lancet Oncol. 2005 Jun;6(6):369-76. link to original article contains protocol PubMed
  4. Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, Rost A, Neuhaus H, Haag C, Clemens M, Heinrich B, Vehling-Kaiser U, Fuchs M, Fleckenstein D, Gesierich W, Uthgenannt D, Einsele H, Holstege A, Hinke A, Schalhorn A, Wilkowski R. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 2006 Aug 20;24(24):3946-52. link to original article contains verified regimen PubMed
  5. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23. link to original article contains verified protocol PubMed
  6. SAKK 44/00-CECOG/PAN.1.3.001: Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W; Swiss Group for Clinical Cancer Research; Central European Cooperative Oncology Group. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 2007 Jun 1;25(16):2212-7. link to original article contains verified protocol PubMed
    1. CBR/QoL analysis: Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R; Central European Cooperative Oncology Group. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol. 2008 Aug 1;26(22):3695-701. link to original article contains verified protocol PubMed
  7. ECOG E6201: Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O'Dwyer P, Haller D, Catalano P, Cella D, Benson AB 3rd. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009 Aug 10;27(23):3778-85. Epub 2009 Jul 6. link to original article contains verified protocol link to PMC article PubMed
  8. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20;27(33):5513-8. Epub 2009 Oct 26. link to original article contains verified protocol PubMed
  9. GIP-1: Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F; Gruppo Oncologico Italia Meridionale (GOIM).; Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente (GISCAD).; Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC). Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010 Apr 1;28(10):1645-51. link to original article contains protocol PubMed
  10. SWOG S0205: Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, Rowland KM, Atkins JN, Mirtsching BC, Rivkin SE, Khorana AA, Goldman B, Fenoglio-Preiser CM, Abbruzzese JL, Blanke CD. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010 Aug 1;28(22):3605-10. Epub 2010 Jul 6. link to original article contains verified protocol link to PMC article PubMed
  11. Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, Funakoshi A, Furuse J, Park YS, Ohkawa S, Springett GM, Wasan HS, Trask PC, Bycott P, Ricart AD, Kim S, Van Cutsem E. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol. 2011 Mar;12(3):256-62. link to original article contains verified protocol PubMed
  12. PRODIGE 4/ACCORD 11: Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. link to original article contains verified protocol PubMed
    1. QoL analysis: Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Boige V, Bérille J, Conroy T. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol. 2013 Jan 1;31(1):23-9. Epub 2012 Dec 3. link to original article PubMed
  13. GEST: Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. Epub 2013 Apr 1. link to original article contains verified protocol PubMed
  14. MPACT: Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. Epub 2013 Oct 16. link to original article contains verified protocol link to PMC article PubMed
  15. Hong JY, Nam EM, Lee J, Park JO, Lee SC, Song SY, Choi SH, Heo JS, Park SH, Lim HY, Kang WK, Park YS. Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients. Cancer Chemother Pharmacol. 2014 Jan;73(1):125-30. Epub 2013 Oct 27. link to original article contains verified protocol PubMed
  16. GAMMA: Fuchs CS, Azevedo S, Okusaka T, Van Laethem JL, Lipton LR, Riess H, Szczylik C, Moore MJ, Peeters M, Bodoky G, Ikeda M, Melichar B, Nemecek R, Ohkawa S, Świeboda-Sadlej A, Tjulandin SA, Van Cutsem E, Loberg R, Haddad V, Gansert JL, Bach BA, Carrato A. A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Ann Oncol. 2015 May;26(5):921-7. Epub 2015 Jan 21. contains verified protocol link to PMC article PubMed
  17. Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, Marsh R, Wallace J, Kozloff M, Rajdev L, Cohen D, Wade J, Sleckman B, Lenz HJ, Stiff P, Kumar P, Xu P, Henderson L, Takebe N, Salgia R, Wang X, Stadler WM, de Sauvage FJ, Kindler HL. Randomized phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol. 2015 Dec 20;33(36):4284-92. Epub 2015 Nov 2. link to original article contains protocol in supplement link to PMC article PubMed
  18. Lee HS, Chung MJ, Park JY, Bang S, Park SW, Kim HG, Noh MH, Lee SH, Kim YT, Kim HJ, Kim CD, Lee DK, Cho KB, Cho CM, Moon JH, Kim DU, Kang DH, Cheon YK, Choi HS, Kim TH, Kim JK, Moon J, Shin HJ, Song SY; Korean Society of Gastrointestinal Cancer. A randomized, multicenter, phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea. Medicine (Baltimore). 2017 Jan;96(1):e5702. contains verified protocol link to PMC article PubMed
  19. ViP: Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, Evans A, Shaw VE, Wadsley J, Valle JW, Propper D, Wasan H, Falk S, Cunningham D, Coxon F, Ross P, Madhusudan S, Wadd N, Corrie P, Hickish T, Costello E, Campbell F, Rawcliffe C, Neoptolemos JP. Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncol. 2017 Apr;18(4):486-499. Epub 2017 Mar 2. link to original article contains protocol PubMed

GemOx

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GemOx: Gemcitabine, Oxaliplatin

Regimen

Study Evidence Comparator Efficacy
Louvet et al. 2005 Phase III Gemcitabine Seems to have superior PFS
Poplin et al. 2009 (E6201) Phase III Gemcitabine Seems not superior
Gemcitabine, FDR Not reported

Chemotherapy

14-day cycles

References

  1. Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A; GERCOR; GISCAD. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005 May 20;23(15):3509-16. link to original article contains verified protocol PubMed
  2. Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O'Dwyer P, Haller D, Catalano P, Cella D, Benson AB 3rd. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009 Aug 10;27(23):3778-85. Epub 2009 Jul 6. link to original article contains verified protocol link to PMC article PubMed

Gemcitabine & nab-Paclitaxel

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Variant #1

Study Evidence Comparator Efficacy
Von Hoff et al. 2013 (MPACT) Phase III Gemcitabine Superior OS

Chemotherapy

  • Gemcitabine (Gemzar) as follows, given second:
    • Cycle 1: 1000 mg/m2 IV once per day on days 1, 8, 15, 29, 36, 43
    • Cycle 2 onwards: 1000 mg/m2 IV once per day on days 1, 8, 15
  • Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows, given first:
    • Cycle 1: 125 mg/m2 IV over 30 to 40 minutes once per day on days 1, 8, 15, 29, 36, 43
    • Cycle 2 onwards: 125 mg/m2 IV over 30 to 40 minutes once per day on days 1, 8, 15

8-week cycle followed by 28-day cycles until disease progression or intolerance

Variant #2

Study Evidence
Von Hoff et al. 2011 Phase II

Note: The abstract and body of Von Hoff et al. 2011 contradicted each other about which drug is given first in this regimen.

Chemotherapy

28-day cycles

References

  1. Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. Epub 2011 Oct 3. link to original article contains verified protocol link to PMC article PubMed
  2. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. Epub 2013 Oct 16. link to original article contains verified protocol link to PMC article PubMed

GTX

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GTX: Gemcitabine, Taxotere (Docetaxel), Xeloda (Capecitabine)

Regimen

Study Evidence
Fine et al. 2007 Retrospective

Note: De Jesus-Acosta et al. 2012 lists the capecitabine dose as "750 mg/m2/day orally divided into two doses," but this is believed to be a typographical error since the original reference that it cites, Fine et al. 2007, uses capecitabine at 750 mg/m2 PO BID. The 2009 ASCO abstract by Fine also lists this 750 mg/m2 PO BID (1500 mg/m2/day) dose.

Chemotherapy

21-day cycles

References

  1. Retrospective: Fine RL, Fogelman DR, Schreibman SM, Desai M, Sherman W, Strauss J, Guba S, Andrade R, Chabot J. The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis. Cancer Chemother Pharmacol. 2008 Jan;61(1):167-75. Epub 2007 Apr 18. link to original article contains protocol PubMed
  2. Abstract: R. L. Fine, G. Moorer, W. Sherman, K. Chu, M. Maurer, J. Chabot, I. Postolov, J. Prowda, S. Schreibman, J. Levitz. Phase II trial of GTX chemotherapy in metastatic pancreatic cancer. 2009 ASCO Annual Meeting abstract 4623. link to abstract content property of HemOnc.org
  3. Retrospective: De Jesus-Acosta A, Oliver GR, Blackford A, Kinsman K, Flores EI, Wilfong LS, Zheng L, Donehower RC, Cosgrove D, Laheru D, Le DT, Chung K, Diaz LA Jr. A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2012 Feb;69(2):415-24. Epub 2011 Jul 29. link to original article contains verified protocol--with error as noted above link to PMC article PubMed

S-1 monotherapy

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Regimen

Study Evidence Comparator Efficacy
Ueno et al. 2013 (GEST) Phase III (E) Gemcitabine Non-inferior OS
Gemcitabine & S-1 Not reported

Chemotherapy

  • Tegafur, gimeracil, oteracil (S-1) as follows:
    • BSA less than 1.25 m2: 40 mg PO BID on days 1 to 28
    • BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO BID on days 1 to 28
    • BSA 1.5 m2 or more: 60 mg PO BID on days 1 to 28

42-day cycles

References

  1. GEST: Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. Epub 2013 Apr 1. link to original article contains verified protocol PubMed

Metastatic disease, refractory

Best supportive care

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Regimen

Study Evidence Comparator Efficacy
Pelzer et al. 2011 (CONKO) Phase III OFF Inferior OS

Best supportive care. Placed here because one or more randomized clinical trials included a best supportive care arm in this disease context.

References

  1. Pelzer U, Schwaner I, Stieler J, Adler M, Seraphin J, Dörken B, Riess H, Oettle H. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer. 2011 Jul;47(11):1676-81. Epub 2011 May 10. link to original article contains verified protocol--with error as noted above PubMed

Capecitabine & Erlotinib

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Regimen

Study Evidence
Kulke et al. 2007 Phase II

Chemotherapy

21-day cycles

References

  1. Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007 Oct 20;25(30):4787-92. link to original article contains verified protocol PubMed

CapeOx

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CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda (Capecitabine), OXaliplatin

Regimen

Study Evidence
Xiong et al. 2008 Phase II

Chemotherapy

21-day cycles

References

  1. Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, Wolff RA. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer. 2008 Oct 15;113(8):2046-52. link to original article contains verified protocol PubMed

Fluorouracil, Folinic acid, nanoliposomal Irinotecan

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Regimen

Study Evidence Comparator Efficacy
Wang-Gillam et al. 2015 (NAPOLI-01) Phase III Fluorouracil & Folinic acid Seems to have superior OS
Irinotecan, nanoliposomal Not reported

Chemotherapy

  • Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1 after folinic acid
  • Folinic acid (Leucovorin) 400 mg/m2 IV over 30 minutes once on day 1, given prior to fluorouracil
  • Irinotecan liposome (Onivyde) 70 mg/m2 (irinotecan free base) IV over 90 minutes once on day 1, given first
    • Per Wang-Gillam et al. 2015 (NAPOLI-01), 70 mg/m2 irinotecan free base is equivalent to 80 mg/m2 nanoliposomal irinotecan. According to the trial's ClinicalTrials.gov page: "The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 80 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 70 mg/ m2 of irinotecan free base."

14-day cycles

References

  1. Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-57. Epub 2015 Nov 29. Erratum in: Lancet. 2016 Feb 6;387(10018):536. link to original article contains verified protocol PubMed

FOLFIRI

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FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan

Variant #1

Study Evidence
Zaniboni et al. 2012 (GISCAD) Phase II

Chemotherapy

14-day cycles

Variant #2, modified FOLFIRI.3

Study Evidence Comparator Efficacy
Yoo et al. 2009 Randomized Phase II mFOLFOX Seems not superior

Chemotherapy

14-day cycles

References

  1. Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ, Kim SC, Lee JL. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009 Nov 17;101(10):1658-63. Epub 2009 Oct 13. link to original article contains protocol link to PMC article PubMed
  2. Zaniboni A, Aitini E, Barni S, Ferrari D, Cascinu S, Catalano V, Valmadre G, Ferrara D, Veltri E, Codignola C, Labianca R. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. Cancer Chemother Pharmacol. 2012 Jun;69(6):1641-5. Epub 2012 May 11. link to original article contains protocol PubMed

FOLFOX

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

Regimen

Study Evidence Comparator Efficacy
Yoo et al. 2009 Randomized Phase II mFOLFIRI.3 Seems not superior

Chemotherapy

14-day cycles

References

  1. Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ, Kim SC, Lee JL. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009 Nov 17;101(10):1658-63. Epub 2009 Oct 13. link to original article contains protocol link to PMC article PubMed

OFF

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OFF: Oxaliplatin, Fluorouracil, Folinic acid

Regimen

Study Evidence Comparator Efficacy
Pelzer et al. 2011 (CONKO) Phase III Best supportive care Superior OS
Oettle et al. 2014 (CONKO-003) Phase III Fluorouracil & Folinic acid Superior OS

Note: The treatment section of Pelzer et al. 2011 incorrectly lists the oxaliplatin dose as "0.85 g/m2," or 850 mg/m2.

Chemotherapy

42-day cycles

References

  1. Pelzer U, Schwaner I, Stieler J, Adler M, Seraphin J, Dörken B, Riess H, Oettle H. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer. 2011 Jul;47(11):1676-81. Epub 2011 May 10. link to original article contains verified protocol--with error as noted above PubMed
  2. Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, Görner M, Mölle M, Greten TF, Lakner V, Bischoff S, Sinn M, Dörken B, Pelzer U. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014 Aug 10;32(23):2423-9. Epub 2014 Jun 30. link to original article contains verified protocol PubMed

Olaparib monotherapy

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Regimen

Study Evidence
Kaufman et al. 2014 Phase II

Patients had germline BRCA1/2 mutations and had previously received gemcitabine.

Chemotherapy

Continued until progression

References

  1. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article contains verified protocol PubMed

Paclitaxel, nanoparticle albumin-bound monotherapy

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Regimen

Study Evidence
Hosein et al. 2013 Phase II

Chemotherapy

28-day cycles

References

  1. Hosein PJ, de Lima Lopes G Jr, Pastorini VH, Gomez C, Macintyre J, Zayas G, Reis I, Montero AJ, Merchan JR, Rocha Lima CM. A phase II trial of nab-paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am J Clin Oncol. 2013 Apr;36(2):151-6. Epub 2012 Feb 2. link to original article contains protocol PubMed
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