Topotecan is active against Wilms' tumor: Results of a multi-institutional phase II study

Purpose A phase II study was conducted to evaluate the activity and safety of topotecan in pediatric patients with recurrent Wilms' tumor. Patients and Methods Patients with favorable histology Wilms' tumor ( FHWT) and recurrence after at least one salvage chemotherapy regimen or with anaplastic histology Wilms' tumor ( AHWT) in first or subsequent recurrence were eligible. Patients were stratified according to histology, with statistical considerations based on the FHWT stratum. Topotecan was administered intravenously over 30 minutes for 5 days on 2 consecutive weeks. Treatment dosages were adjusted to achieve a target area under the curve ( AUC) of 80 +/- 10 ng/mL*h. Tumor responses were measured after two cycles of treatment. Results Thirty-seven patients ( 26 patients with FHWT) were enrolled and received a total of 94 cycles of topotecan ( range, one to six cycles). The median topotecan dosage required to achieve the target AUC was 1.8 mg/m(2) ( range, 0.7 to 3.2 mg/m(2)). Of 25 assessable patients with FHWT, 12 had partial response ( PR), six had stable disease (SD), and seven had progressive disease ( PD), for an overall response rate of 48% ( 95% CI, 27.8% to 68.7%). Of 11 assessable patients with AHWT, two had PR, one had SD, and eight had PD. The main toxicities were grade 3 and 4 neutropenia ( median duration, 13 days) and thrombocytopenia ( median duration, 7.5 days). Conclusion Topotecan administered on a protracted schedule is active against recurrent FHWT. Inclusion of topotecan in front-line clinical trials for patients with recurrent Wilms' tumor should be considered.