Hepatoblastoma

Section editor transclusions

7 regimens on this page 7 variants on this page

High-risk, upfront therapy

COG AHEP0731 protocol W

Protocol

Study	Years of enrollment	Evidence
Katzenstein et al. 2017 (COG AHEP0731)	9/2009-2/2012	Non-randomized

References

1. 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. link to original article link to PMC article PubMed NCT00980460

SIOPEL-4 protocol

Protocol

Study	Years of enrollment	Evidence
Zsiros et al. 2013 (SIOPEL-4)	1/1/2005-8/31/2009	Non-randomized

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 PubMed NCT00077389

Adjuvant therapy

Cisplatin & Fluorouracil (CF) & Vincristine

Regimen

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

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 cycle for 1 cycle (to be given within 42 days of resection)

References

1. 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 monotherapy

Regimen

Study	Years 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
Brock et al. 2018 (SIOPEL 6)	2007-2014	Phase 3 (C)	Cisplatin & Sodium thiosulfate		More hearing loss

Chemotherapy

• Cisplatin (Platinol)

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 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

Cisplatin & Doxorubicin

PLADO: PLAtinol (Cisplatin) & DOxorubicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Ortega et al. 2000	1989-1992	Phase 3 (E-switch-ic)	CF & Vincristine		More toxic
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

Chemotherapy

• Cisplatin (Platinol)
• Doxorubicin (Adriamycin)

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 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