Journal of Clinical Oncology, Vol 12, 1969-1973, Copyright © 1994 by American Society of Clinical Oncology
Phase I trial of continuous infusion carboplatin and etoposide in children with refractory acute leukemia: a Pediatric Oncology Group study
PD Sadowitz, R Dubowy, A Souid, BH Pollock, H Weinstein, RT Parmley, WP Bowman, V Land, T Vats and C Pratt
Department of Pediatrics, State University of New York, Health Science Center, Syracuse.
PURPOSE: The purpose of this phase I study was to determine the toxicities
and response to continuous infusion carboplatin in combination with a fixed
dose of etoposide (VP-16) in children with refractory acute leukemia.
PATIENTS AND METHODS: From January 1989 to February 1992, 20 patients
received 28 courses of treatment. Each course of treatment consisted of a
1-hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed
by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day
dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg
increments to a final, total dose of 1,875 mg/m2 over 5 days. RESULTS:
Significant marrow suppression was observed in all patients, with prolonged
marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred
in three patients; 10 patients experienced life-threatening infection and
three had severe thrombocytopenic bleeding. Major marrow responses (two
complete remissions and two partial remissions) occurred in four patients
(20%). CONCLUSION: In view of the apparent antileukemic efficacy and
minimal extramedullary toxicity, carboplatin deserves further study in a
phase II trial.