Hepatoblastoma

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

Last updated on 2024-07-23: 10 regimens on this page 10 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

1. 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

1. 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

1. 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 dosing details in manuscript have been reviewed by our editors 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

1. 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 dosing details in manuscript have been reviewed by our editors 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

1. 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 dosing details in manuscript have been reviewed by our editors 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

1. 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

1. 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

1. 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00003912
2. 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 IV 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

1. 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: Cycle length 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

1. 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 dosing details in manuscript have been reviewed by our editors PubMed
2. 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
3. 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