Phase I trial of continuous infusion carboplatin and etoposide in children with refractory acute leukemia: a Pediatric Oncology Group study.
OBJECTIVE
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.


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%).


CONCLUSIONS
In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.
Sadowitz
P D
PD
Department of Pediatrics, State University of New York, Health Science Center, Syracuse.
Dubowy
R
R
Souid
A
A
Pollock
B H
BH
Weinstein
H
H
Parmley
R T
RT
Bowman
W P
WP
Land
V
V
Vats
T
T
Pratt
C
C
D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007239:Infections / Q000150:complications; D007262:Infusions, Intravenous / Q000379:methods; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D012074:Remission Induction; D014481:United States
D005047:Etoposide; D016190:Carboplatin