Phase II study of a protracted irinotecan schedule in children with refractory of recurrent soft tissue sarcoma.

BACKGROUND: Irinotecan (CPT-11) is a novel antineoplastic agent that takes effect by inhibiting topoisomerase I. The Italian Soft Tissue Sarcoma (STS) Committee performed a multiinstitutional Phase II study to evaluate its effect on STS. METHODS: Over a 2-year period between 2002 and 2004, 32 heavily pretreated patients were administered 60-minute infusions of irinotecan at 20 mg/m2/day, for 5 days a week, for 2 consecutive weeks. The courses were repeated every 4 weeks for at least 2 courses, unless there were signs of toxicity or disease progression. Thirty patients, 13 with peripheral primitive neuroectodermal tumor (PNET), 12 with rhabdomyosarcoma (RMS), 3 with desmoplastic small round cell tumor (DSRCT), and 2 with other STS were evaluable for response. RESULTS: A total of 79 cycles were delivered. The main regimen-related toxicity was diarrhea, occurring in 58% of cycles with 9 episodes graded as 3 or 4. Grade 3-4 neutropenia was recorded in 10% of cycles. The overall response rate was 23% (2 complete remissions +5 partial remissions of 30 patients), 38% for PNET and 16% for RMS. In addition, 4 minor responses were noted. CONCLUSIONS: As a single agent in the treatment of recurrent and refractory STS, irinotecan administered on a daily x5 x2 schedule revealed a noteworthy response rate in a population of heavily pretreated patients, especially in the subset of patients with PNET. Its hematologic toxicity profile warrants further investigation in association with other myelotoxic agents.