Topotecan in the treatment of refractory neuroblastoma and other malignant tumors in childhood -: a phase-II-study

Background: The topoisomerase-l-inhibitor Topotecan (TPT) has shown a broad activity in the therapy of adult malignant diseases. In pediatric oncology TPT has been rarely used. Methods: From 1/98 to 8/99 we conducted a multicenter phase-II-study of TPT (1.5 mg/m(2)/d in 30 min i.v. for 5 days every 21 days) in pediatric patients (pts) with malignant tumors refractory to conventional therapy (either second line or any relapse). Patients: A total of 20 pts received 81 cycles. The 7 female and 13 male pts had a median age of 10.2 years at the beginning of the TPT therapy. Results: The median number of administered TPT cycles was 4 with an interval of 23.5 days. The median administered TPT dose was 1.48 mg/m(2)/d. No complete responses, but 2 partial responses and 9 stable diseases were observed. In 9 pts the disease progressed. The mean duration until progression for SD was 130 and not different from PR with 131 days. The median cumulative TPT dose until progression in responders was 30 mg/m(2). For all study-pts the median overall survival time was 235 days with 1 pt. still alive. The main toxicity was hematological with anemia grade III/IV (10/42% of all evaluable TPT cycles), neutropenia grade III/IV (49/18%) and thrombopenia grade III/IV (35/36%). Non-hematologic toxicity was mild with the exception of 4 cycles with infection grade III and I grade IV. No patient died of therapy-related complications. Conclusions: TPT as monotherapy has shown an antitumor activity in pediatric pts with various malignancies. Toxicity was mainly hematological and manageable. Further evaluation of TPT treatment is planned using combinations with other cytostatic drugs.