IFOSFAMIDE CARBOPLATIN ETOPOSIDE (ICE) FOR RECURRENT MALIGNANT SOLID TUMORS OF CHILDHOOD - A PEDIATRIC-ONCOLOGY-GROUP PHASE I/II STUDY

Purpose: The combination of ifosfamide (I) and etoposide (E) was useful in salvaging patients with recurrent/resistant malignant solid tumors of childhood. Carboplatin (C), active against a number of pediatric cancers, was added to I and E to form a three-drug combination called ICE to improve the response rate. Patients and Methods: ICE, consisting of I 1.5 g/m(2) plus E 100 mg/m(2) i.v.q.d. X 3 plus C i.v. on day 3 only, was given in 21-28-day intervals. C was started at 300 mg/m(2), and the dose was escalated in 25% increments, with three evaluable patients treated at each level. Results: Ninety-two patients were enrolled in this phase I/II study between July 1990 and April 1993. A total of 331 courses of ICE was administered. Median courses of ICE received were three (range, 1-16). The maximum tolerated dose (MTD) for C when used in combination was found to be 635 mg/m(2). The response rate for ICE at the MTD for C was complete response (CR) 26% and CR + partial response (PR) 53%. The response was even better in those who received C at the MTD: 32% achieving a CR and 63% a CR + PR. Pancytopenia was the dose-limiting toxicity. Thirteen episodes of bacterial infection were reported, none fatal. Only one patient developed a Fanconi-like syndrome. Conclusion: The MTD of C when used with I and E was found to be 635 mg/m(2). The overall CR + PR rate for all patients treated at all C dose levels was 53%. Best responses were seen in non-Hodgkin's lymphoma, neuroblastoma, soft tissue sarcomas, and Wilms' tumor. Myelosuppression was the predominant toxicity and was dose limiting.