Hepatoblastoma

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 Elaine Fan, MD
University of Utah
Salt Lake City, UT
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5 regimens on this page
6 variants on this page


High-risk, upfront therapy

COG AHEP0731 protocol H

Protocol, Responders

Chemotherapy, VIT (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 once per day on days 1 & 8
    • ≥ 10 kg: 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:
    • < 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/m2 (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
  • Temsirolimus (Torisel) by the following weight-based criteria:
    • < 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
    • ≥ 10 kg: 35 mg/m2 IV over 30 minutes once per day on days 1 & 8

21-day course

Chemotherapy, C5VD (Cycles 3 to 6)

  • Cisplatin (Platinol) by the following weight-based criteria:
    • < 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
    • ≥ 10 kg: 100 mg/m2 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
    • ≥ 10 kg: 600 mg/m2 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 once per day on days 2, 9, 16
    • ≥ 10 kg: 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:
    • < 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
    • ≥ 10 kg: 30 mg/m2 IV over 15 minutes once per day on days 1 & 2

Dexrazoxane (Zinecard) omitted for cycles 3 to 6

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 once per day on days 1 & 8
    • ≥ 10 kg: 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:
    • < 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/m2 (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
  • Temsirolimus (Torisel) by the following weight-based criteria:
    • < 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
    • ≥ 10 kg: 35 mg/m2 IV over 30 minutes once per day on days 1 & 8

21-day course

Chemotherapy, C5VD (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
    • ≥ 10 kg: 100 mg/m2 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
    • ≥ 10 kg: 600 mg/m2 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 once per day on days 2, 9, 16
    • ≥ 10 kg: 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:
    • < 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
    • ≥ 10 kg: 30 mg/m2 IV over 15 minutes once per day on days 1 & 2
  • Dexrazoxane (Zinecard) by the following weight-based criteria:
    • < 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
    • ≥ 10 kg: 300 mg/m2 IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2

21-day cycle

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 once per day on days 1 & 8
    • ≥ 10 kg: 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:
    • < 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/m2 (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
  • Temsirolimus (Torisel) by the following weight-based criteria:
    • < 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
    • ≥ 10 kg: 35 mg/m2 IV over 30 minutes once per day on days 1 & 8

21-day course

Protocol, Non-Responders

Chemotherapy, VIT (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 once per day on days 1 & 8
    • ≥ 10 kg: 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:
    • < 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/m2 (maximum dose of 100 mg) IV over 90 minutes once per day on days 1 to 5
  • Temsirolimus (Torisel) by the following weight-based criteria:
    • < 10 kg: 1.2 mg/kg IV over 30 minutes once per day on days 1 & 8
    • ≥ 10 kg: 35 mg/m2 IV over 30 minutes once per day on days 1 & 8

21-day course

Chemotherapy, C5VD (Cycles 3 to 6)

  • Cisplatin (Platinol) by the following weight-based criteria:
    • < 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
    • ≥ 10 kg: 100 mg/m2 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
    • ≥ 10 kg: 600 mg/m2 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 once per day on days 2, 9, 16
    • ≥ 10 kg: 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:
    • < 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
    • ≥ 10 kg: 30 mg/m2 IV over 15 minutes once per day on days 1 & 2

Dexrazoxane (Zinecard) omitted for cycles 3 to 6

Chemotherapy, C5VD (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
    • ≥ 10 kg: 100 mg/m2 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
    • ≥ 10 kg: 600 mg/m2 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 once per day on days 2, 9, 16
    • ≥ 10 kg: 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:
    • < 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
    • ≥ 10 kg: 30 mg/m2 IV over 15 minutes once per day on days 1 & 2
  • Dexrazoxane (Zinecard) by the following weight-based criteria:
    • < 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
    • ≥ 10 kg: 300 mg/m2 IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2

21-day cycle

References

  1. None yet identified

COG AHEP0731 protocol W

Protocol

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

To be completed

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 PubMed Clinical Trial Registry

SIOPEL-4 protocol

Protocol

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

To be completed

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 Clinical Trial Registry

Intermediate-Risk, Upfront Therapy

COG AHEP0731 protocol F

Protocol

Chemotherapy, C5VD (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
    • ≥ 10 kg: 100 mg/m2 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
    • ≥ 10 kg: 600 mg/m2 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 once per day on days 2, 9, 16
    • ≥ 10 kg: 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:
    • < 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
    • ≥ 10 kg: 30 mg/m2 IV over 15 minutes once per day on days 1 & 2

Dexrazoxane (Zinecard) omitted for cycles 1 to 4

21-day cycle

Chemotherapy, C5VD (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
    • ≥ 10 kg: 100 mg/m2 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
    • ≥ 10 kg: 600 mg/m2 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 once per day on days 2, 9, 16
    • ≥ 10 kg: 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:
    • < 10 kg: 1 mg/kg IV over 15 minutes once per day on days 1 & 2
    • ≥ 10 kg: 30 mg/m2 IV over 15 minutes once per day on days 1 & 2
  • Dexrazoxane (Zinecard) by the following weight-based criteria:
    • < 10 kg: 10 mg/kg IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2
    • ≥ 10 kg: 300 mg/m2 IV over 5 to 15 minutes immediately prior to doxorubicin on days 1 & 2

21-day cycle

References

  1. Not yet identified

Low-Risk, Upfront Therapy

COG AHEP0731 protocol T

Protocol

Chemotherapy, adjuvant C5V (2 cycles)

  • Cisplatin (Platinol) by the following weight-based criteria:
    • < 10 kg: 3.3 mg/kg IV over 6 hours once on day 1
    • ≥ 10 kg: 100 mg/m2 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
    • ≥ 10 kg: 600 mg/m2 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 once per day on days 2, 9, 16
    • ≥ 10 kg: 1.5 mg/m2 (maximum dose of 2 mg) IV push or infusion once per day on days 2, 9, 16

21-day cycle

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; 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. link to original article link to PMC article PubMed Clinical Trial Registry

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

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

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. 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 Clinical Trial Registry

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

Chemotherapy

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 Clinical Trial Registry
  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 Clinical Trial Registry

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
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

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 Clinical Trial Registry
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