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

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/m2 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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 18 Pg. 2879-84 (Jun 20 2006) ISSN: 1527-7755 [Electronic] United States
• PMID: 16782927 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Granulocyte Colony-Stimulating Factor
• Vincristine
• Carboplatin
• Cisplatin
• Fluorouracil

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Child
• Child, Preschool
• Cisplatin (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Hepatoblastoma (drug therapy)
• Humans
• Infant
• Liver Neoplasms (drug therapy)
• Male
• Vincristine (administration & dosage)