Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma

Marcio H. Malogolowkin*, Howard Katzenstein, Mark D. Krailo, Zhengjia Chen, Laura Bowman, Marleta Reynolds, Milton Finegold, Brian Greffe, Jon Rowland, Kurt Newman, Richard B. Womer, Wendy B. London, Robert P. Castleberry

*Corresponding author for this work

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Purpose: The INT-0098 Intergroup Liver Tumor Study demonstrated no statistically significant differences in event-free and overall survival between patients randomized to treatment with either cisplatin + fluorouracil + vincristine (C5V) or cisplatin + doxorubicin. Results from this and other therapeutic trials suggested that cisplatin was the most active agent against hepatoblastoma. To increase the platinum dose-intensity, a novel regimen was developed alternating carboplatin and cisplatin (CC) every 2 weeks. The P9645 study was designed to compare the risk of treatment failure for patients with stage III/IV hepatoblastoma randomized to either C5V or CC. Methods: C5V was given according to INT-0098 and CC consisted of carboplatin at 700 mg/m 2 on day 0 (560 mg/m2 after two cycles) followed by cisplatin 100 mg/m2 on day 14. Granulocyte colony-stimulating factor was used after each CC cycle. All patients received four to six cycles of chemotherapy. Results: From the time the study was opened until the time that random assignment was halted, 56 patients received CC and 53 patients received C5V. The 1-year event-free survival was 37% for patients receiving CC and 57% for those receiving C5V (P = .017). Patients randomly assigned to CC required more blood product support. As a result of a semiannual review by the Children's Oncology Group Data and Safety Monitoring Committee, random assignment was discontinued after 3 years of enrollment because the projected improvement in long-term outcome associated with CC was statistically excluded as a possible outcome of this trial. Conclusion: Intensification of therapy by alternating platinum analogs increased the risk of adverse outcome in children with unresectable or metastatic hepatoblastoma.

Original languageEnglish (US)
Pages (from-to)2879-2884
Number of pages6
JournalJournal of Clinical Oncology
Volume24
Issue number18
DOIs
StatePublished - Jun 20 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Malogolowkin, M. H., Katzenstein, H., Krailo, M. D., Chen, Z., Bowman, L., Reynolds, M., Finegold, M., Greffe, B., Rowland, J., Newman, K., Womer, R. B., London, W. B., & Castleberry, R. P. (2006). Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma. Journal of Clinical Oncology, 24(18), 2879-2884. https://doi.org/10.1200/JCO.2005.02.6013