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	Elaine Fan, MD KU School of Medicine Wichita, KS, USA LinkedIn

7 regimens on this page 7 variants on this page

High-risk, upfront therapy

COG AHEP0731 protocol H - responders

Regimen

Chemotherapy, VIT portion (cycles 1 & 2)

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8

Irinotecan (Camptosar) by the following weight-based criteria:
- Less than 10 kg: 1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
- 10 kg or more: 50 mg/m² (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5

Targeted therapy, VIT portion (cycles 1 & 2)

Temsirolimus (Torisel) by the following weight-based criteria:
- Less than 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
- 10 kg or more: 35 mg/m² IV over 30 minutes once per day on days 1 & 8

Chemotherapy, C5VD portion (cycles 3 to 6)

Cisplatin (Platinol) by the following weight-based criteria:
- Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
- 10 kg or more: 100 mg/m² IV once over 6 hours on day 1

Fluorouracil (5-FU) by the following weight-based criteria:
- Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
- 10 kg or more: 600 mg/m² IV push over 2 to 4 minutes once on day 2

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16

Doxorubicin (Adriamycin) by the following weight-based criteria:
- Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
- 10 kg or more: 30 mg/m² IV over 15 minutes once per day on days 1 & 2

Chemotherapy, VIT portion (cycle 7)

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8

Irinotecan (Camptosar) by the following weight-based criteria:
- Less than 10 kg: 1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
- 10 kg or more: 50 mg/m² (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5

Targeted therapy, VIT portion (cycle 7)

Temsirolimus (Torisel) by the following weight-based criteria:
- Less than 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
- 10 kg or more: 35 mg/m² IV over 30 minutes once per day on days 1 & 8

Chemotherapy, C5VD portion (cycles 8 & 9)

Cisplatin (Platinol) by the following weight-based criteria:
- Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
- 10 kg or more: 100 mg/m² IV once over 6 hours on day 1

Fluorouracil (5-FU) by the following weight-based criteria:
- Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
- 10 kg or more: 600 mg/m² IV push over 2 to 4 minutes once on day 2

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16

Doxorubicin (Adriamycin) by the following weight-based criteria:
- Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
- 10 kg or more: 30 mg/m² IV over 15 minutes once per day on days 1 & 2

Supportive therapy, C5VD portion (cycles 8 & 9)

Dexrazoxane (Zinecard) by the following weight-based criteria:
- Less than 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
- 10 kg or more: 300 mg/m² IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2

Chemotherapy, VIT portion (cycle 10)

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8

Irinotecan (Camptosar) by the following weight-based criteria:
- Less than 10 kg: 1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
- 10 kg or more: 50 mg/m² (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5

Targeted therapy, VIT portion (cycle 10)

Temsirolimus (Torisel) by the following weight-based criteria:
- Less than 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
- 10 kg or more: 35 mg/m² IV over 30 minutes once per day on days 1 & 8

21-day cycle for 10 cycles

References

None yet identified

COG AHEP0731 protocol H - non-responders

Regimen

Chemotherapy, VIT portion (cycles 1 & 2)

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8

Irinotecan (Camptosar) by the following weight-based criteria:
- Less than 10 kg: 1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
- 10 kg or more: 50 mg/m² (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5

Targeted therapy, VIT portion (cycles 1 & 2)

Temsirolimus (Torisel) by the following weight-based criteria:
- Less than 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
- 10 kg or more: 35 mg/m² IV over 30 minutes once per day on days 1 & 8

Chemotherapy, C5VD portion (cycles 3 to 6)

Cisplatin (Platinol) by the following weight-based criteria:
- Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
- 10 kg or more: 100 mg/m² IV once over 6 hours on day 1

Fluorouracil (5-FU) by the following weight-based criteria:
- Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
- 10 kg or more: 600 mg/m² IV push over 2 to 4 minutes once on day 2

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16

Doxorubicin (Adriamycin) by the following weight-based criteria:
- Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
- 10 kg or more: 30 mg/m² IV over 15 minutes once per day on days 1 & 2

Chemotherapy, C5VD portion (cycles 7 to 8)

Cisplatin (Platinol) by the following weight-based criteria:
- Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
- 10 kg or more: 100 mg/m² IV once over 6 hours on day 1

Fluorouracil (5-FU) by the following weight-based criteria:
- Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
- 10 kg or more: 600 mg/m² IV push over 2 to 4 minutes once on day 2

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16

Doxorubicin (Adriamycin) by the following weight-based criteria:
- Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
- 10 kg or more: 30 mg/m² IV over 15 minutes once per day on days 1 & 2

Supportive therapy, C5VD portion (cycles 7 to 8)

Dexrazoxane (Zinecard) by the following weight-based criteria:
- Less than 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
- 10 kg or more: 300 mg/m² IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2

21-day cycle for 8 cycles

References

None yet identified

COG AHEP0731 protocol W

Regimen

Study	Dates of enrollment	Evidence
Katzenstein et al. 2017 (COG AHEP0731 HR)	2009-09 to 2012-02	Non-randomized

Chemotherapy

Irinotecan (Camptosar) by the following weight-based criteria:
- Less than 10 kg: 1.67 mg/kg IV over 90 minutes once per day on days 1 to 5
- 10 kg or more: 50 mg/m² IV over 90 minutes once per day on days 1 to 5
Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg IV once per day on days 1 & 8
- 10 kg or more: 1.5 mg/m² IV once per day on days 1 & 8

21-day cycle for 2 cycles

Subsequent treatment

Depends on response; see paper for details

References

COG AHEP0731 HR: Katzenstein HM, Furman WL, Malogolowkin MH, Krailo MD, McCarville MB, Towbin AJ, Tiao GM, Finegold MJ, Ranganathan S, Dunn SP, Langham MR, McGahren ED, Rodriguez-Galindo C, Meyers RL. Upfront window vincristine/irinotecan treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 study committee. Cancer. 2017 Jun 15;123(12):2360-2367. Epub 2017 Feb 17. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00980460

SIOPEL-4 protocol, resectable after A3

Study	Dates of enrollment	Evidence
Zsiros et al. 2013 (SIOPEL-4)	2005-01-01 to 2009-08-31	Non-randomized

Neoadjuvant, "Cycles A1, A2, A3"

Chemotherapy

Cisplatin (Platinol) as follows:
- Cycle 1: 80 mg/m² IV continuous infusion over 24 hours, started on day 1, then 70 mg/m² IV continuous infusion over 24 hours, started on days 8 & 15 (total dose: 220 mg/m²)
- Cycle 2: 70 mg/m² IV continuous infusion over 24 hours, started on days 1, 8, 15 (total dose: 210 mg/m²)
- Cycle 3: 70 mg/m² IV continuous infusion over 24 hours, started on days 1 & 8 (total dose: 140 mg/m²)
Doxorubicin (Adriamycin) as follows:
- Cycles 1 & 2: 30 mg/m²/day IV continuous infusion over 48 hours, started on day 8 (total dose per cycle: 60 mg/m²)
- Cycle 3: 30 mg/m²/day IV continuous infusion over 48 hours, started on day 1 (total dose: 60 mg/m²)

28-day cycle for 3 cycles, followed by determination of resectability, then:

Definitive

Local therapy

Surgical resection, including liver transplantation and metastasectomy, if needed

Adjuvant, "Cycle C"

Chemotherapy

Carboplatin (Paraplatin) AUC 6.6 IV over 60 minutes once on day 1
Doxorubicin (Adriamycin) 20 mg/m²/day IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 40 mg/m²)

21-day cycle for 3 cycles

References

SIOPEL-4: Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, Branchereau S, Aronson D, Rangaswami A, Ronghe M, Casanova M, Sullivan M, Morland B, Czauderna P, Perilongo G; International Childhood Liver Tumours Strategy Group (SIOPEL). Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 2013 Aug;14(9):834-42. Epub 2013 Jul 4. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00077389

SIOPEL-4 protocol, unresectable after A3

Study	Dates of enrollment	Evidence
Zsiros et al. 2013 (SIOPEL-4)	2005-01-01 to 2009-08-31	Non-randomized

Neoadjuvant, "Cycles A1, A2, A3"

Chemotherapy

Cisplatin (Platinol) as follows:
- Cycle 1: 80 mg/m² IV continuous infusion over 24 hours, started on day 1, then 70 mg/m² IV continuous infusion over 24 hours, started on days 8 & 15 (total dose: 220 mg/m²)
- Cycle 2: 70 mg/m² IV continuous infusion over 24 hours, started on days 1, 8, 15 (total dose: 210 mg/m²)
- Cycle 3: 70 mg/m² IV continuous infusion over 24 hours, started on days 1 & 8 (total dose: 140 mg/m²)
Doxorubicin (Adriamycin) as follows:
- Cycles 1 & 2: 30 mg/m²/day IV continuous infusion over 48 hours, started on day 8 (total dose per cycle: 60 mg/m²)
- Cycle 3: 30 mg/m²/day IV continuous infusion over 48 hours, started on day 1 (total dose: 60 mg/m²)

28-day cycle for 3 cycles, followed by determination of unresectability, then:

Neoadjuvant, "Cycle B"

Chemotherapy

Carboplatin (Paraplatin) AUC 10.6 IV over 60 minutes once on day 1
Doxorubicin (Adriamycin) 25 mg/m²/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 75 mg/m²)

21-day cycle for 2 cycles, followed by:

Definitive

Local therapy

Surgical resection, including liver transplantation and metastasectomy, if needed

References

SIOPEL-4: Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, Branchereau S, Aronson D, Rangaswami A, Ronghe M, Casanova M, Sullivan M, Morland B, Czauderna P, Perilongo G; International Childhood Liver Tumours Strategy Group (SIOPEL). Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 2013 Aug;14(9):834-42. Epub 2013 Jul 4. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00077389

Intermediate-risk, upfront therapy

COG AHEP0731 protocol F

Regimen

Chemotherapy, C5VD portion (cycles 1 to 4)

Cisplatin (Platinol) by the following weight-based criteria:
- Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
- 10 kg or more: 100 mg/m² IV once over 6 hours on day 1

Fluorouracil (5-FU) by the following weight-based criteria:
- Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
- 10 kg or more: 600 mg/m² IV push over 2 to 4 minutes once on day 2

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16

Doxorubicin (Adriamycin) by the following weight-based criteria:
- Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
- 10 kg or more: 30 mg/m² IV over 15 minutes once per day on days 1 & 2

Chemotherapy, C5VD portion (cycles 5 & 6)

Cisplatin (Platinol) by the following weight-based criteria:
- Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
- 10 kg or more: 100 mg/m² IV once over 6 hours on day 1

Fluorouracil (5-FU) by the following weight-based criteria:
- Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
- 10 kg or more: 600 mg/m² IV push over 2 to 4 minutes once on day 2

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16

Doxorubicin (Adriamycin) by the following weight-based criteria:
- Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
- 10 kg or more: 30 mg/m² IV over 15 minutes once per day on days 1 & 2

Supportive therapy, C5VD portion (cycles 5 & 6)

Dexrazoxane (Zinecard) by the following weight-based criteria:
- Less than 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
- 10 kg or more: 300 mg/m² IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2

21-day cycle for 6 cycles

References

Not yet identified

Low-risk, upfront therapy

COG AHEP0731 protocol T

Regimen

Preceding treatment

Surgical resection

Chemotherapy

Cisplatin (Platinol) by the following weight-based criteria:
- Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
- 10 kg or more: 100 mg/m² IV once over 6 hours on day 1

Fluorouracil (5-FU) by the following weight-based criteria:
- Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
- 10 kg or more: 600 mg/m² IV push over 2 to 4 minutes once on day 2

Vincristine (Oncovin) by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16

21-day cycle for 2 cycles

References

COG AHEP0731: Katzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, Finegold MJ, Ranganathan S, Dunn S, McGahren ED, Tiao GM, O'Neill AF, Qayed M, Furman WL, Xia C, Rodriguez-Galindo C, Meyers RL; Children's Oncology Group. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncology. 2019 May 1. 20(5) 719-727. Epub 2019 Apr 8. link to original article link to PMC article PubMed NCT00980460

Neoadjuvant therapy

Cisplatin monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Perilongo et al. 2009 (SIOPEL 3)	1998-2006	Phase 3 (E-de-esc)	Cisplatin & Doxorubicin	Non-inferior complete resection rate (primary endpoint)
Brock et al. 2018 (SIOPEL 6)	2007-2014	Phase 3 (C)	Cisplatin & Sodium thiosulfate		More hearing loss

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV continuous infusion over 24 hours, started on day 1

14-day cycle for 4 cycles

References

SIOPEL 3: Perilongo G, Maibach R, Shafford E, Brugieres L, Brock P, Morland B, de Camargo B, Zsiros J, Roebuck D, Zimmermann A, Aronson D, Childs M, Widing E, Laithier V, Plaschkes J, Pritchard J, Scopinaro M, MacKinlay G, Czauderna P. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med. 2009 Oct 22;361(17):1662-70. link to original article contains dosing details in manuscript PubMed NCT00003912
SIOPEL 6: Brock PR, Maibach R, Childs M, Rajput K, Roebuck D, Sullivan MJ, Laithier V, Ronghe M, Dall'Igna P, Hiyama E, Brichard B, Skeen J, Mateos ME, Capra M, Rangaswami AA, Ansari M, Rechnitzer C, Veal GJ, Covezzoli A, Brugières L, Perilongo G, Czauderna P, Morland B, Neuwelt EA. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med. 2018 Jun 21;378(25):2376-2385. link to original article link to PMC article PubMed NCT00652132

Adjuvant therapy

Cisplatin & Fluorouracil (CF) & Vincristine

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Katzenstein et al. 2019 (COG AHEP0731)	2010-2014	Phase 3 (E-esc)	Observation	Seems to have superior EFS (primary endpoint)

For stage 1 or 2 hepatoblastoma without 100% pure fetal stage I or small-cell undifferentiated histology with complete resection at diagnosis and no history of prior chemotherapy or liver directed therapy. Eligible patients include: patients< 21 years old, elevated serum α-fetoprotein level (>100 ng/mL), at least 50% Karnofsky (patients >16 years) or Lansky (patients ≤16 years) performance status.

Preceding treatment

Curative surgical resection

Chemotherapy

Cisplatin (Platinol) by the following weight-based criteria:
- Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
- 10 kg or more: 100 mg/m² over 6 hours once on day 1
Fluorouracil by the following weight-based criteria:
- Less than 10 kg: 20 mg/kg IV once on day 2
- 10 kg or more: 600 mg/m² IV once on day 2
Vincristine by the following weight-based criteria:
- Less than 10 kg: 0.05 mg/kg IV once per day on days 2, 9, 16
- 10 kg or more: 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 2, 9, 16

21-day course; to be given within 42 days of resection

References

COG AHEP0731: Katzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, Finegold MJ, Ranganathan S, Dunn S, McGahren ED, Tiao GM, O'Neill AF, Qayed M, Furman WL, Xia C, Rodriguez-Galindo C, Meyers RL; Children's Oncology Group. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncology. 2019 May 1. 20(5) 719-727. Epub 2019 Apr 8. link to original article link to PMC article PubMed NCT00980460

All lines of therapy

Cisplatin & Doxorubicin

PLADO: PLAtinol (Cisplatin) & DOxorubicin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Ortega et al. 2000	1989-1992	Phase 3 (E-switch-ic)	CF & Vincristine		More toxic (primary endpoint)
Pritchard et al. 2000 (SIOPEL 1)	1990-1994	Non-randomized
Perilongo et al. 2009 (SIOPEL 3)	1998-2006	Phase 3 (C)	Cisplatin	Non-inferior complete resection rate

Note: the duration of cycles was not specified.'

Chemotherapy

Cisplatin (Platinol) by the following age-based criteria:
- Younger than 1 year old: 3 mg/kg IV over 6 hours once on day 1, given first
- 1 year old or older: 90 mg/m² IV over 6 hours once on day 1, given first
Doxorubicin (Adriamycin) 20 mg/m²/day IV continuous infusion over 96 hours, started on day 1, given second (total dose per cycle: 80 mg/m²)

4 cycles

References

Ortega JA, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Finegold MJ, Haas JE, King DR, Liu-Mares W, Sensel MG, Krailo MD; Children's Cancer Group; Pediatric Oncology Group. Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group. J Clin Oncol. 2000 Jul;18(14):2665-75. link to original article contains dosing details in manuscript PubMed
SIOPEL 1: Pritchard J, Brown J, Shafford E, Perilongo G, Brock P, Dicks-Mireaux C, Keeling J, Phillips A, Vos A, Plaschkes J. Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol. 2000 Nov 15;18(22):3819-28. link to original article PubMed
SIOPEL 3: Perilongo G, Maibach R, Shafford E, Brugieres L, Brock P, Morland B, de Camargo B, Zsiros J, Roebuck D, Zimmermann A, Aronson D, Childs M, Widing E, Laithier V, Plaschkes J, Pritchard J, Scopinaro M, MacKinlay G, Czauderna P. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med. 2009 Oct 22;361(17):1662-70. link to original article PubMed NCT00003912

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 =High-risk, upfront therapy=
-==COG AHEP0731 protocol H {{#subobject:3a8i39|Regimen=1}}==
+==COG AHEP0731 protocol H - responders {{#subobject:3a8i39|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Protocol, Responders {{#subobject:a15cb47|Variant=1}}===
+===Regimen {{#subobject:a15cb47|Variant=1}}===
-====Chemotherapy, VIT (Cycles 1 through 2)====
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, VIT portion (cycles 1 & 2)====
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 1, 8
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 1, 8
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
 *[[Irinotecan (Camptosar)]] by the following weight-based criteria:
-** < 10 kg:1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes on days 1 through 5
+**Less than 10 kg: 1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
-** ≥ 10 kg:50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 90 minutes on days 1 through 5
+**10 kg or more: 50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
+====Targeted therapy, VIT portion (cycles 1 & 2)====
 *[[Temsirolimus (Torisel)]] by the following weight-based criteria:
-** < 10 kg:1.2 mg/kg IV over 30 minutes on days 1, 8
+**Less than 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
-** ≥ 10 kg:35 mg/m<sup>2</sup> IV over 30 minutes on days 1, 8
+**10 kg or more: 35 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
-'''21 day course'''
+====Chemotherapy, C5VD portion (cycles 3 to 6)====
-====Chemotherapy, C5VD (Cycles 3 through 6)====
 *[[Cisplatin (Platinol)]] by the following weight-based criteria:
-** < 10 kg:3.3 mg/kg IV over 6 hours once on day 1
+**Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
-** ≥ 10 kg:100 mg/m<sup>2</sup> IV once over 6 hours on day 1
+**10 kg or more: 100 mg/m<sup>2</sup> IV once over 6 hours on day 1
 *[[Fluorouracil (5-FU)]] by the following weight-based criteria:
-** < 10 kg:20 mg/kg IV push over 2 to 4 minutes once on day 2
+**Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
-** ≥ 10 kg:600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
+**10 kg or more: 600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
 *[[Doxorubicin (Adriamycin)]] by the following weight-based criteria:
-** < 10 kg:1 mg/kg IV over 15 minutes on days 1, 2
+**Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
-** ≥ 10 kg:30 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2
+**10 kg or more: 30 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 & 2
-'''[[Dexrazoxane (Zinecard)]] omitted for cycles 3 through 6'''
+====Chemotherapy, VIT portion (cycle 7)====
-'''21 day cycle'''
-====Chemotherapy, VIT (Cycle 7)====
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 1, 8
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 1, 8
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
 *[[Irinotecan (Camptosar)]] by the following weight-based criteria:
-** < 10 kg:1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes on days 1 through 5
+**Less than 10 kg: 1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
-** ≥ 10 kg:50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 90 minutes on days 1 through 5
+**10 kg or more: 50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
+====Targeted therapy, VIT portion (cycle 7)====
 *[[Temsirolimus (Torisel)]] by the following weight-based criteria:
-** < 10 kg:1.2 mg/kg IV over 30 minutes on days 1, 8
+**Less than 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
-** ≥ 10 kg:35 mg/m<sup>2</sup> IV over 30 minutes on days 1, 8
+**10 kg or more: 35 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
-'''21 day course'''
-====Chemotherapy, C5VD (Cycles 8 through 9)====
+====Chemotherapy, C5VD portion (cycles 8 & 9)====
 *[[Cisplatin (Platinol)]] by the following weight-based criteria:
-** < 10 kg:3.3 mg/kg IV over 6 hours once on day 1
+**Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
-** ≥ 10 kg:100 mg/m<sup>2</sup> IV once over 6 hours on day 1
+**10 kg or more: 100 mg/m<sup>2</sup> IV once over 6 hours on day 1
 *[[Fluorouracil (5-FU)]] by the following weight-based criteria:
-** < 10 kg:20 mg/kg IV push over 2 to 4 minutes once on day 2
+**Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
-** ≥ 10 kg:600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
+**10 kg or more: 600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
 *[[Doxorubicin (Adriamycin)]] by the following weight-based criteria:
-** < 10 kg:1 mg/kg IV over 15 minutes on days 1, 2
+**Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
-** ≥ 10 kg:30 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2
+**10 kg or more: 30 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 & 2
+====Supportive therapy, C5VD portion (cycles 8 & 9)====
 *[[Dexrazoxane (Zinecard)]] by the following weight-based criteria:
-** < 10 kg:10 mg/kg IV over 5 to 15 minutes immediately prior to [[Doxorubicin (Adriamycin)]] on days 1, 2
+**Less than 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
-** ≥ 10 kg:300 mg/m<sup>2</sup> IV over 5 to 15 minutes immediately prior to [[Doxorubicin (Adriamycin)]] on days 1, 2
+**10 kg or more: 300 mg/m<sup>2</sup> IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
-'''21 day cycle'''
+====Chemotherapy, VIT portion (cycle 10)====
-====Chemotherapy, VIT (Cycle 10)====
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 1, 8
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 1, 8
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
 *[[Irinotecan (Camptosar)]] by the following weight-based criteria:
-** < 10 kg:1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes on days 1 through 5
+**Less than 10 kg: 1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
-** ≥ 10 kg:50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 90 minutes on days 1 through 5
+**10 kg or more: 50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
+====Targeted therapy, VIT portion (cycle 10)====
 *[[Temsirolimus (Torisel)]] by the following weight-based criteria:
-** < 10 kg:1.2 mg/kg IV over 30 minutes on days 1, 8
+**Less than 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
-** ≥ 10 kg:35 mg/m<sup>2</sup> IV over 30 minutes on days 1, 8
+**10 kg or more: 35 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
-'''21 day course'''
+'''21-day cycle for 10 cycles'''
+</div></div>
+===References===
+#None yet identified
-===Protocol, Non-Responders {{#subobject:a15cb47|Variant=2}}===
+==COG AHEP0731 protocol H - non-responders {{#subobject:3a882f|Regimen=1}}==
-====Chemotherapy, VIT (Cycle 1 through 2)====
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:a15cb47|Variant=2}}===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, VIT portion (cycles 1 & 2)====
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 1, 8
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 1, 8
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 1 & 8
 *[[Irinotecan (Camptosar)]] by the following weight-based criteria:
-** < 10 kg:1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes on days 1 through 5
+**Less than 10 kg: 1.67 mg/kg (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
-** ≥ 10 kg:50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 90 minutes on days 1 through 5
+**10 kg or more: 50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
+====Targeted therapy, VIT portion (cycles 1 & 2)====
 *[[Temsirolimus (Torisel)]] by the following weight-based criteria:
-** < 10 kg:1.2 mg/kg IV over 30 minutes on days 1, 8
+**Less than 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
-** ≥ 10 kg:35 mg/m<sup>2</sup> IV over 30 minutes on days 1, 8
+**10 kg or more: 35 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
-'''21 day course'''
+====Chemotherapy, C5VD portion (cycles 3 to 6)====
-====Chemotherapy, C5VD (Cycles 3 through 6)====
 *[[Cisplatin (Platinol)]] by the following weight-based criteria:
-** < 10 kg:3.3 mg/kg IV over 6 hours once on day 1
+**Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
-** ≥ 10 kg:100 mg/m<sup>2</sup> IV once over 6 hours on day 1
+**10 kg or more: 100 mg/m<sup>2</sup> IV once over 6 hours on day 1
 *[[Fluorouracil (5-FU)]] by the following weight-based criteria:
-** < 10 kg:20 mg/kg IV push over 2 to 4 minutes once on day 2
+**Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
-** ≥ 10 kg:600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
+**10 kg or more: 600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
 *[[Doxorubicin (Adriamycin)]] by the following weight-based criteria:
-** < 10 kg:1 mg/kg IV over 15 minutes on days 1, 2
+**Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
-** ≥ 10 kg:30 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2
+**10 kg or more: 30 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 & 2
-'''[[Dexrazoxane (Zinecard)]] omitted for cycles 3 through 6'''
-====Chemotherapy, C5VD (Cycles 7 through 8)====
+====Chemotherapy, C5VD portion (cycles 7 to 8)====
 *[[Cisplatin (Platinol)]] by the following weight-based criteria:
-** < 10 kg:3.3 mg/kg IV over 6 hours once on day 1
+**Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
-** ≥ 10 kg:100 mg/m<sup>2</sup> IV once over 6 hours on day 1
+**10 kg or more: 100 mg/m<sup>2</sup> IV once over 6 hours on day 1
 *[[Fluorouracil (5-FU)]] by the following weight-based criteria:
-** < 10 kg:20 mg/kg IV push over 2 to 4 minutes once on day 2
+**Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
-** ≥ 10 kg:600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
+**10 kg or more: 600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
 *[[Doxorubicin (Adriamycin)]] by the following weight-based criteria:
-** < 10 kg:1 mg/kg IV over 15 minutes on days 1, 2
+**Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
-** ≥ 10 kg:30 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2
+**10 kg or more: 30 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 & 2
+====Supportive therapy, C5VD portion (cycles 7 to 8)====
 *[[Dexrazoxane (Zinecard)]] by the following weight-based criteria:
-** < 10 kg:10 mg/kg IV over 5 to 15 minutes immediately prior to [[Doxorubicin (Adriamycin)]] on days 1, 2
+**Less than 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
-** ≥ 10 kg:300 mg/m<sup>2</sup> IV over 5 to 15 minutes immediately prior to [[Doxorubicin (Adriamycin)]] on days 1, 2
+**10 kg or more: 300 mg/m<sup>2</sup> IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
-'''21 day cycle'''
+'''21-day cycle for 8 cycles'''
+</div></div>
+===References===
+#None yet identified
-===References===
 ==COG AHEP0731 protocol W {{#subobject:3a8i39|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:a15cb47|Variant=1}}===
+===Regimen {{#subobject:a15cb47|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
@@ Line 170: / Line 169: @@
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5665173/ Katzenstein et al. 2017 (COG AHEP0731)]
+|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5665173/ Katzenstein et al. 2017 (COG AHEP0731 HR)]
 |2009-09 to 2012-02
 | style="background-color:#91cf61" |Non-randomized
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Irinotecan (Camptosar)]] by the following weight-based criteria:
+**Less than 10 kg: 1.67 mg/kg IV over 90 minutes once per day on days 1 to 5
+**10 kg or more: 50 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 to 5
+*[[Vincristine (Oncovin)]] by the following weight-based criteria:
+**Less than 10 kg: 0.05 mg/kg IV once per day on days 1 & 8
+**10 kg or more: 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
+'''21-day cycle for 2 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*Depends on response; see paper for details
 </div></div>
 ===References===
-#'''COG AHEP0731:''' Katzenstein HM, Furman WL, Malogolowkin MH, Krailo MD, McCarville MB, Towbin AJ, Tiao GM, Finegold MJ, Ranganathan S, Dunn SP, Langham MR, McGahren ED, Rodriguez-Galindo C, Meyers RL. Upfront window vincristine/irinotecan treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 study committee. Cancer. 2017 Jun 15;123(12):2360-2367. Epub 2017 Feb 17. [https://doi.org/10.1002/cncr.30591 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5665173/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28211941/ PubMed] NCT00980460
+#'''COG AHEP0731 HR:''' Katzenstein HM, Furman WL, Malogolowkin MH, Krailo MD, McCarville MB, Towbin AJ, Tiao GM, Finegold MJ, Ranganathan S, Dunn SP, Langham MR, McGahren ED, Rodriguez-Galindo C, Meyers RL. Upfront window vincristine/irinotecan treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 study committee. Cancer. 2017 Jun 15;123(12):2360-2367. Epub 2017 Feb 17. [https://doi.org/10.1002/cncr.30591 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5665173/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28211941/ PubMed] [https://clinicaltrials.gov/study/NCT00980460 NCT00980460]
-==SIOPEL-4 protocol {{#subobject:3a6ad9|Regimen=1}}==
+==SIOPEL-4 protocol, resectable after A3 {{#subobject:3a6ad9|Regimen=1}}==
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3730732/ Zsiros et al. 2013 (SIOPEL-4)]
+|2005-01-01 to 2009-08-31
+| style="background-color:#91cf61" |Non-randomized
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
+===Neoadjuvant, "Cycles A1, A2, A3" {{#subobject:59db47|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] as follows:
+**Cycle 1: 80 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1, then 70 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 8 & 15 (total dose: 220 mg/m<sup>2</sup>)
+**Cycle 2: 70 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 8, 15 (total dose: 210 mg/m<sup>2</sup>)
+**Cycle 3: 70 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1 & 8 (total dose: 140 mg/m<sup>2</sup>)
+*[[Doxorubicin (Adriamycin)]] as follows:
+**Cycles 1 & 2: 30 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 8 (total dose per cycle: 60 mg/m<sup>2</sup>)
+**Cycle 3: 30 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 1 (total dose: 60 mg/m<sup>2</sup>)
+'''28-day cycle for 3 cycles, followed by determination of resectability, then:'''
+</div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:59db47|Variant=1}}===
+===Definitive===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Local therapy====
+*[[Surgery#Surgical_resection|Surgical resection]], including liver transplantation and [[Surgery#Metastasectomy|metastasectomy]], if needed
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Adjuvant, "Cycle C"===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6.6 IV over 60 minutes once on day 1
+*[[Doxorubicin (Adriamycin)]] 20 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
+'''21-day cycle for 3 cycles'''
+</div></div></div>
+===References===
+#'''SIOPEL-4:''' Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, Branchereau S, Aronson D, Rangaswami A, Ronghe M, Casanova M, Sullivan M, Morland B, Czauderna P, Perilongo G; International Childhood Liver Tumours Strategy Group (SIOPEL). Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 2013 Aug;14(9):834-42. Epub 2013 Jul 4. [https://doi.org/10.1016/s1470-2045(13)70272-9 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3730732/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23831416/ PubMed] [https://clinicaltrials.gov/study/NCT00077389 NCT00077389]
+==SIOPEL-4 protocol, unresectable after A3 {{#subobject:3aund9|Regimen=1}}==
+<div class="toccolours" style="background-color:#c8a2c8">
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
@@ Line 192: / Line 245: @@
 |-
 |}
-</div></div>
+<div class="toccolours" style="background-color:#eeeeee">
+===Neoadjuvant, "Cycles A1, A2, A3" {{#subobject:5c4c47|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] as follows:
+**Cycle 1: 80 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1, then 70 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 8 & 15 (total dose: 220 mg/m<sup>2</sup>)
+**Cycle 2: 70 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 8, 15 (total dose: 210 mg/m<sup>2</sup>)
+**Cycle 3: 70 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1 & 8 (total dose: 140 mg/m<sup>2</sup>)
+*[[Doxorubicin (Adriamycin)]] as follows:
+**Cycles 1 & 2: 30 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 8 (total dose per cycle: 60 mg/m<sup>2</sup>)
+**Cycle 3: 30 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 1 (total dose: 60 mg/m<sup>2</sup>)
+'''28-day cycle for 3 cycles, followed by determination of unresectability, then:'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Neoadjuvant, "Cycle B"===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 10.6 IV over 60 minutes once on day 1
+*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 75 mg/m<sup>2</sup>)
+'''21-day cycle for 2 cycles, followed by:'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Definitive===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Local therapy====
+*[[Surgery#Surgical_resection|Surgical resection]], including liver transplantation and [[Surgery#Metastasectomy|metastasectomy]], if needed
+</div></div></div>
 ===References===
-#'''SIOPEL-4:''' Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, Branchereau S, Aronson D, Rangaswami A, Ronghe M, Casanova M, Sullivan M, Morland B, Czauderna P, Perilongo G; International Childhood Liver Tumours Strategy Group (SIOPEL). Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 2013 Aug;14(9):834-42. Epub 2013 Jul 4. [https://doi.org/10.1016/s1470-2045(13)70272-9 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3730732/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23831416/ PubMed] NCT00077389
+#'''SIOPEL-4:''' Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, Branchereau S, Aronson D, Rangaswami A, Ronghe M, Casanova M, Sullivan M, Morland B, Czauderna P, Perilongo G; International Childhood Liver Tumours Strategy Group (SIOPEL). Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 2013 Aug;14(9):834-42. Epub 2013 Jul 4. [https://doi.org/10.1016/s1470-2045(13)70272-9 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3730732/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23831416/ PubMed] [https://clinicaltrials.gov/study/NCT00077389 NCT00077389]
-=Intermediate-Risk, Upfront Therapy=
+=Intermediate-risk, upfront therapy=
 ==COG AHEP0731 protocol F {{#subobject:3a8i39|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:a15cb47|Variant=1}}===
+===Regimen {{#subobject:a15cb47|Variant=1}}===
-====Chemotherapy, C5VD (Cycles 1 through 4)====
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, C5VD portion (cycles 1 to 4)====
 *[[Cisplatin (Platinol)]] by the following weight-based criteria:
-** < 10 kg:3.3 mg/kg IV over 6 hours once on day 1
+**Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
-** ≥ 10 kg:100 mg/m<sup>2</sup> IV once over 6 hours on day 1
+**10 kg or more: 100 mg/m<sup>2</sup> IV once over 6 hours on day 1
 *[[Fluorouracil (5-FU)]] by the following weight-based criteria:
-** < 10 kg:20 mg/kg IV push over 2 to 4 minutes once on day 2
+**Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
-** ≥ 10 kg:600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
+**10 kg or more: 600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
 *[[Doxorubicin (Adriamycin)]] by the following weight-based criteria:
-** < 10 kg:1 mg/kg IV over 15 minutes on days 1, 2
+**Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
-** ≥ 10 kg:30 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2
+**10 kg or more: 30 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 & 2
-'''[[Dexrazoxane (Zinecard)]] omitted for cycles 1 through 4'''
-'''21 day cycle'''
-====Chemotherapy, C5VD (Cycles 5 through 6)====
+====Chemotherapy, C5VD portion (cycles 5 & 6)====
 *[[Cisplatin (Platinol)]] by the following weight-based criteria:
-** < 10 kg:3.3 mg/kg IV over 6 hours once on day 1
+**Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
-** ≥ 10 kg:100 mg/m<sup>2</sup> IV once over 6 hours on day 1
+**10 kg or more: 100 mg/m<sup>2</sup> IV once over 6 hours on day 1
 *[[Fluorouracil (5-FU)]] by the following weight-based criteria:
-** < 10 kg:20 mg/kg IV push over 2 to 4 minutes once on day 2
+**Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
-** ≥ 10 kg:600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
+**10 kg or more: 600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
 *[[Doxorubicin (Adriamycin)]] by the following weight-based criteria:
-** < 10 kg:1 mg/kg IV over 15 minutes on days 1, 2
+**Less than 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
-** ≥ 10 kg:30 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2
+**10 kg or more: 30 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 & 2
+====Supportive therapy, C5VD portion (cycles 5 & 6)====
 *[[Dexrazoxane (Zinecard)]] by the following weight-based criteria:
-** < 10 kg:10 mg/kg IV over 5 to 15 minutes immediately prior to [[Doxorubicin (Adriamycin)]] on days 1, 2
+**Less than 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
-** ≥ 10 kg:300 mg/m<sup>2</sup> IV over 5 to 15 minutes immediately prior to [[Doxorubicin (Adriamycin)]] on days 1, 2
+**10 kg or more: 300 mg/m<sup>2</sup> IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
-'''21 day cycle'''
+'''21-day cycle for 6 cycles'''
+</div></div>
+===References===
+#Not yet identified
-===References===
+=Low-risk, upfront therapy=
-= Low-Risk, Upfront Therapy=
 ==COG AHEP0731 protocol T {{#subobject:3a8i39|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Protocol {{#subobject:a15cb47|Variant=1}}===
+===Regimen {{#subobject:a15cb47|Variant=1}}===
-====Chemotherapy, adjuvant C5V (2 cycles)====
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Surgical_resection|Surgical resection]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
 *[[Cisplatin (Platinol)]] by the following weight-based criteria:
-** < 10 kg:3.3 mg/kg IV over 6 hours once on day 1
+**Less than 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
-** ≥ 10 kg:100 mg/m<sup>2</sup> IV once over 6 hours on day 1
+**10 kg or more: 100 mg/m<sup>2</sup> IV once over 6 hours on day 1
 *[[Fluorouracil (5-FU)]] by the following weight-based criteria:
-** < 10 kg:20 mg/kg IV push over 2 to 4 minutes once on day 2
+**Less than 10 kg: 20 mg/kg IV push over 2 to 4 minutes once on day 2
-** ≥ 10 kg:600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
+**10 kg or more: 600 mg/m<sup>2</sup> IV push over 2 to 4 minutes once on day 2
 *[[Vincristine (Oncovin)]] by the following weight-based criteria:
-** < 10 kg:0.05 mg/kg (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**Less than 10 kg: 0.05 mg/kg (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
-** ≥ 10 kg:1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion on days 2, 9, 16
+**10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16
-'''21 day cycle'''
+'''21-day cycle for 2 cycles'''
+</div></div>
+===References===
+#'''COG AHEP0731:''' Katzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, Finegold MJ, Ranganathan S, Dunn S, McGahren ED, Tiao GM, O'Neill AF, Qayed M, Furman WL, Xia C, Rodriguez-Galindo C, Meyers RL; Children's Oncology Group. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncology. 2019 May 1. 20(5) 719-727. Epub 2019 Apr 8. [https://doi.org/10.1016/S1470-2045(18)30895-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6499702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30975630/ PubMed] [https://clinicaltrials.gov/study/NCT00980460 NCT00980460]
+=Neoadjuvant therapy=
+==Cisplatin monotherapy {{#subobject:ea894c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:9134b2|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
+!style="width: 15%"|Dates of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://doi.org/10.1056/NEJMoa0810613 Perilongo et al. 2009 (SIOPEL 3)]
+|1998-2006
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[#Cisplatin_.26_Doxorubicin|Cisplatin & Doxorubicin]]
+| style="background-color:#eeee01" |Non-inferior complete resection rate (primary endpoint)
+|
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6117111/ Brock et al. 2018 (SIOPEL 6)]
+|2007-2014
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cisplatin_.26_Sodium_thiosulfate_999|Cisplatin & Sodium thiosulfate]]
+|
+| style="background-color:#d73027" |More hearing loss
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+'''14-day cycle for 4 cycles'''
+</div></div>
 ===References===
-#'''COG AHEP0731:''' Katzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, Finegold MJ, Ranganathan S, Dunn S, McGahren ED, Tiao GM, O'Neill AF, Qayed M, Furman WL, Xia C, Rodriguez-Galindo C, Meyers RL; Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): A Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):719-27. [https://doi.org/10.1016/S1470-2045(18)30895-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30975630/ PubMed] NCT00003912
+# '''SIOPEL 3:''' Perilongo G, Maibach R, Shafford E, Brugieres L, Brock P, Morland B, de Camargo B, Zsiros J, Roebuck D, Zimmermann A, Aronson D, Childs M, Widing E, Laithier V, Plaschkes J, Pritchard J, Scopinaro M, MacKinlay G, Czauderna P. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med. 2009 Oct 22;361(17):1662-70. [https://doi.org/10.1056/NEJMoa0810613 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19846851/ PubMed] [https://clinicaltrials.gov/study/NCT00003912 NCT00003912]
+# '''SIOPEL 6:''' Brock PR, Maibach R, Childs M, Rajput K, Roebuck D, Sullivan MJ, Laithier V, Ronghe M, Dall'Igna P, Hiyama E, Brichard B, Skeen J, Mateos ME, Capra M, Rangaswami AA, Ansari M, Rechnitzer C, Veal GJ, Covezzoli A, Brugières L, Perilongo G, Czauderna P, Morland B, Neuwelt EA. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med. 2018 Jun 21;378(25):2376-2385. [https://doi.org/10.1056/nejmoa1801109 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6117111/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29924955/ PubMed] [https://clinicaltrials.gov/study/NCT00652132 NCT00652132]
 =Adjuvant therapy=
@@ Line 278: / Line 397: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6499702/ Katzenstein et al. 2019 (AHEP0731)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6499702/ Katzenstein et al. 2019 (COG AHEP0731)]
 |2010-2014
 | style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#Observation|Observation]]
-| style="background-color:#91cf60" |Seems to have superior EFS
+| style="background-color:#91cf60" |Seems to have superior EFS (primary endpoint)
 |-
 |}
@@ Line 301: / Line 420: @@
 **Less than 10 kg: 0.05 mg/kg IV once per day on days 2, 9, 16
 **10 kg or more: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 2, 9, 16
-'''21-day cycle for 1 cycle (to be given within 42 days of resection)'''
+'''21-day course; to be given within 42 days of resection'''
 </div></div>
 ===References===
-#'''AHEP0731:''' Katzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, Finegold MJ, Ranganathan S, Dunn S, McGahren ED, Tiao GM, O'Neill AF, Qayed M, Furman WL, Xia C, Rodriguez-Galindo C, Meyers RL; Children's Oncology Group. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncology. 2019 May 1. 20(5) 719-727. Epub 2019 Apr 8. [https://doi.org/10.1016/S1470-2045(18)30895-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6499702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30975630/ PubMed] NCT00980460
+#'''COG AHEP0731:''' Katzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, Finegold MJ, Ranganathan S, Dunn S, McGahren ED, Tiao GM, O'Neill AF, Qayed M, Furman WL, Xia C, Rodriguez-Galindo C, Meyers RL; Children's Oncology Group. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncology. 2019 May 1. 20(5) 719-727. Epub 2019 Apr 8. [https://doi.org/10.1016/S1470-2045(18)30895-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6499702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30975630/ PubMed] [https://clinicaltrials.gov/study/NCT00980460 NCT00980460]
 =All lines of therapy=
-==Cisplatin monotherapy {{#subobject:ea894c|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:9134b2|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
-!style="width: 15%"|Dates of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
-|-
-|[https://doi.org/10.1056/NEJMoa0810613 Perilongo et al. 2009 (SIOPEL 3)]
-|1998-2006
-| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#Cisplatin_.26_Doxorubicin|Cisplatin & Doxorubicin]]
-| style="background-color:#eeee01" |Non-inferior complete resection rate
-|
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6117111/ Brock et al. 2018 (SIOPEL 6)]
-|2007-2014
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Sodium_thiosulfate_99|Cisplatin & Sodium thiosulfate]]
-|
-| style="background-color:#d73027" |More hearing loss
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cisplatin (Platinol)]]
-</div></div>
-===References===
-# '''SIOPEL 3:''' Perilongo G, Maibach R, Shafford E, Brugieres L, Brock P, Morland B, de Camargo B, Zsiros J, Roebuck D, Zimmermann A, Aronson D, Childs M, Widing E, Laithier V, Plaschkes J, Pritchard J, Scopinaro M, MacKinlay G, Czauderna P. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med. 2009 Oct 22;361(17):1662-70. [https://doi.org/10.1056/NEJMoa0810613 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19846851/ PubMed] NCT00003912
-# '''SIOPEL 6:''' Brock PR, Maibach R, Childs M, Rajput K, Roebuck D, Sullivan MJ, Laithier V, Ronghe M, Dall'Igna P, Hiyama E, Brichard B, Skeen J, Mateos ME, Capra M, Rangaswami AA, Ansari M, Rechnitzer C, Veal GJ, Covezzoli A, Brugières L, Perilongo G, Czauderna P, Morland B, Neuwelt EA. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med. 2018 Jun 21;378(25):2376-2385. [https://doi.org/10.1056/nejmoa1801109 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6117111/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29924955/ PubMed] NCT00652132
 ==Cisplatin & Doxorubicin {{#subobject:7bb59c|Regimen=1}}==
 PLADO: '''<u>PLA</u>'''tinol (Cisplatin) & '''<u>DO</u>'''xorubicin
@@ Line 354: / Line 441: @@
 |1989-1992
 | style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Vincristine_88|CF & Vincristine]]
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Vincristine_888|CF & Vincristine]]
 |
-| style="background-color:#d73027" |More toxic
+| style="background-color:#d73027" |More toxic (primary endpoint)
 |-
 |[https://doi.org/10.1200/jco.2000.18.22.3819 Pritchard et al. 2000 (SIOPEL 1)]
@@ Line 373: / Line 460: @@
 |-
 |}
+''Note: the duration of cycles was not specified.'''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]]
+*[[Cisplatin (Platinol)]] by the following age-based criteria:
-*[[Doxorubicin (Adriamycin)]]
+**Younger than 1 year old: 3 mg/kg IV over 6 hours once on day 1, '''given first'''
+**1 year old or older: 90 mg/m<sup>2</sup> IV over 6 hours once on day 1, '''given first'''
+*[[Doxorubicin (Adriamycin)]] 20 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1, '''given second''' (total dose per cycle: 80 mg/m<sup>2</sup>)
+'''4 cycles'''
 </div></div>
 ===References===
-# Ortega JA, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Finegold MJ, Haas JE, King DR, Liu-Mares W, Sensel MG, Krailo MD; Children's Cancer Group; Pediatric Oncology Group. Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group. J Clin Oncol. 2000 Jul;18(14):2665-75. [https://doi.org/10.1200/JCO.2000.18.14.2665 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10894865/ PubMed]
+# Ortega JA, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Finegold MJ, Haas JE, King DR, Liu-Mares W, Sensel MG, Krailo MD; Children's Cancer Group; Pediatric Oncology Group. Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group. J Clin Oncol. 2000 Jul;18(14):2665-75. [https://doi.org/10.1200/JCO.2000.18.14.2665 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10894865/ PubMed]
 # '''SIOPEL 1:''' Pritchard J, Brown J, Shafford E, Perilongo G, Brock P, Dicks-Mireaux C, Keeling J, Phillips A, Vos A, Plaschkes J. Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol. 2000 Nov 15;18(22):3819-28. [https://doi.org/10.1200/jco.2000.18.22.3819 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11078495/ PubMed]
-# '''SIOPEL 3:''' Perilongo G, Maibach R, Shafford E, Brugieres L, Brock P, Morland B, de Camargo B, Zsiros J, Roebuck D, Zimmermann A, Aronson D, Childs M, Widing E, Laithier V, Plaschkes J, Pritchard J, Scopinaro M, MacKinlay G, Czauderna P. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med. 2009 Oct 22;361(17):1662-70. [https://doi.org/10.1056/NEJMoa0810613 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19846851/ PubMed] NCT00003912
+# '''SIOPEL 3:''' Perilongo G, Maibach R, Shafford E, Brugieres L, Brock P, Morland B, de Camargo B, Zsiros J, Roebuck D, Zimmermann A, Aronson D, Childs M, Widing E, Laithier V, Plaschkes J, Pritchard J, Scopinaro M, MacKinlay G, Czauderna P. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med. 2009 Oct 22;361(17):1662-70. [https://doi.org/10.1056/NEJMoa0810613 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19846851/ PubMed] [https://clinicaltrials.gov/study/NCT00003912 NCT00003912]
 [[Category:Hepatoblastoma regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Pediatric solid tumors]]

Difference between revisions of "Hepatoblastoma"

Latest revision as of 00:59, 4 May 2024

High-risk, upfront therapy

COG AHEP0731 protocol H - responders

Regimen

Chemotherapy, VIT portion (cycles 1 & 2)

Targeted therapy, VIT portion (cycles 1 & 2)

Chemotherapy, C5VD portion (cycles 3 to 6)

Chemotherapy, VIT portion (cycle 7)

Targeted therapy, VIT portion (cycle 7)

Chemotherapy, C5VD portion (cycles 8 & 9)

Supportive therapy, C5VD portion (cycles 8 & 9)

Chemotherapy, VIT portion (cycle 10)

Targeted therapy, VIT portion (cycle 10)

References

COG AHEP0731 protocol H - non-responders

Regimen

Chemotherapy, VIT portion (cycles 1 & 2)

Targeted therapy, VIT portion (cycles 1 & 2)

Chemotherapy, C5VD portion (cycles 3 to 6)

Chemotherapy, C5VD portion (cycles 7 to 8)

Supportive therapy, C5VD portion (cycles 7 to 8)

References

COG AHEP0731 protocol W

Regimen

Chemotherapy

Subsequent treatment

References

SIOPEL-4 protocol, resectable after A3

Neoadjuvant, "Cycles A1, A2, A3"

Chemotherapy

Definitive

Local therapy

Adjuvant, "Cycle C"

Chemotherapy

References

SIOPEL-4 protocol, unresectable after A3

Neoadjuvant, "Cycles A1, A2, A3"

Chemotherapy

Neoadjuvant, "Cycle B"

Chemotherapy

Definitive

Local therapy

References

Intermediate-risk, upfront therapy

COG AHEP0731 protocol F

Regimen

Chemotherapy, C5VD portion (cycles 1 to 4)

Chemotherapy, C5VD portion (cycles 5 & 6)

Supportive therapy, C5VD portion (cycles 5 & 6)

References

Low-risk, upfront therapy

COG AHEP0731 protocol T

Regimen

Preceding treatment

Chemotherapy

References

Neoadjuvant therapy

Cisplatin monotherapy

Regimen

Chemotherapy

References

Adjuvant therapy

Cisplatin & Fluorouracil (CF) & Vincristine

Regimen

Preceding treatment

Chemotherapy

References

All lines of therapy

Cisplatin & Doxorubicin

Regimen

Chemotherapy

References

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