PHASE-I TRIAL OF CONTINUOUS-INFUSION CARBOPLATIN AND ETOPOSIDE IN CHILDREN WITH REFRACTORY ACUTE-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP STUDY

Purpose: The purpose of this phase I study was to determine the toxici ties and response to continuous infusion carboplatin in combination wi th a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. Patients and Methods: From January 1989 to February 1992, 2 0 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m(2)/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/m(2)) was esc alated by 250- to 375-mg increments to a final, total dose of 1,875 mg /m(2) over 5 days. Results: Significant marrow suppression was observe d in all patients, with prolonged marrow aplasia at the 1,875-mg/m(2) dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocy topenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). Conclusion: I n view of the apparent antileukemic efficacy extramedullary toxicity, carboplatin deserves further study in a phase II trial. (C) 1994 by Am erican Society of Clinical Oncology.