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. doi: 10.1200/JCO.2000.18.14.2665.

Abstract

Purpose: Previous studies demonstrated that chemotherapy with either cisplatin, vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion doxorubicin (regimen B) improved survival in children with hepatoblastoma. The current trial is a randomized comparison of these two regimens.

Patients and methods: Patients (N = 182) were enrolled onto study between August 1989 and December 1992. After initial surgery, patients with stage I-unfavorable histology (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40) hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n = 81). Patients with stage I-favorable histology (FH; n = 9) were treated with four cycles of doxorubicin alone.

Results: There were no events among patients with stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD = 5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P =.09) with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A versus B. Toxicities were more frequent on regimen B. Patients with stage I-UH, stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD = 4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar for either regimen within disease stages. At postinduction surgery I, patients with stage III or IV disease who were found to be tumor-free had no events; those who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other patients with stage III or IV disease had worse outcome.

Conclusion: Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibiotics, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • Female
  • Fluorouracil / administration & dosage
  • Hepatoblastoma / drug therapy*
  • Hepatoblastoma / pathology
  • Hepatoblastoma / surgery
  • Humans
  • Infant
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Male
  • Neoplasm Staging
  • Proportional Hazards Models
  • Survival Analysis
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Antibiotics, Antineoplastic
  • Vincristine
  • Doxorubicin
  • Cisplatin
  • Fluorouracil

Supplementary concepts

  • AP protocol 1