Phase I topotecan preparative regimen for high-risk neuroblastoma, high-grade glioma, and refractory/recurrent pediatric solid tumors

We evaluated the toxicity and maximum tolerated dose of topotecan in a nove l myeloablative regimen as treatment for high-risk pediatric tumors. Patien ts received an assigned topotecan dosage in combination with fixed doses of carboplatin and thiotepa, followed by autologous hematopoietic stem cells infusion. Topotecan dose was escalated in cohorts of four patients until th e maximum tolerated dose of topotecan was defined or until accrual of 30 pa tients. Pharmacokinetics of topotecan were examined, and event-free surviva l was estimated. We describe preliminary results following treatment of 25 pediatric patients with highrisk solid tumors. (C) 2000 Wiley-Liss, Inc.