A phase I study of irinotecan in pediatric patients: A Pediatric Oncology Group Study

A Phase I trial of irinotecan was performed to determine the maximum tolera ted dose (MTD), the dose-limiting toxicities (DLTs), and the incidence and severity of other toxicities in children with refractory solid tumors. Thir ty-five children received 146 courses of irinotecan administered as a 60-mi n i.v. infusion, daily for 5 days, every 21 days, after premedication with dexamethasone and ondansetron, Doses ranged from 30 mg/m(2) to 65 mg/m(2). An MTD was defined in heavily pretreated and less-heavily pretreated (i.e., two prior chemotherapy regimens, no prior bone marrow transplantation, and no radiation to the spine, skull, ribs, or pelvic bones) patients. Myelosu ppression was the primary DLT in heavily pretreated patients, and diarrhea was the DLT in less-heavily pretreated patients. The MTD in the heavily pre treated patient group was 39 mg/m(2), and the MTD in the less-heavily pretr eated patients was 50 mg/m(2). Non-dose-limiting diarrhea that was well con trolled and of brief duration was observed in approximately 75% of patients . A partial response was observed in one patient with neuroblastoma, and in one patient with hepatocellular carcinoma. Stable disease (4-20 cycles) wa s observed in seven patients with a variety of malignancies including neuro blastoma, pineoblastoma, glioblastoma, brainstem glioma, osteosarcoma, hepa toblastoma, and a central nervous system rhabdoid tumor. In conclusion, the recommended Phase II dose of irinotecan administered as a 60-min i.v. infu sion daily for 5 days, every 21 days, is 39 mg/m(2) in heavily treated and 50 mg/m(2) in less-heavily treated children with solid tumors.