A North Central Cancer Treatment Group phase II trial of topotecan in relapsed gliomas

Current systemic treatment options for patients with relapsed gliomas are l imited. The topoisomerase I inhibitor topotecan has demonstrated broad anti tumor activity in both preclinical studies as well as a number of phase I a nd II trials in humans. Studies in primates have shown good cerebrospinal f luid levels of topotecan following systemic administration. We therefore pe rformed this phase II trial in patients who developed evidence of progressi ve glioma after definitive radiation therapy. Patients were treated with 1. 5 mg/m(2) intravenously daily for 5 consecutive days repeated every three w eeks. For patients who had received prior nitrosourea-containing chemothera py, the starting dose was 1.25 mg/m(2). Thirty-three patients were entered on this study. All patients were eligible and evaluable for both response a nd toxicity. Seven patients experienced grade 4 leukopenia with 2 of these patients dying of infection-related complications. Six of these seven patie nts were not taking anticonvulsants during treatment. Nine patients develop ed grade 3-4 thrombocytopenia, seven of whom were not taking anticonvulsant s. Nonhematologic side effects were infrequent and manageable. One patient experienced a partial response to this treatment for an overall response ra te of 3% (95% binomial confidence interval 0.3%-20.4%). The median time to progression was 14.9 weeks and median survival 19.9 weeks. Topotecan at thi s dose and schedule showed no substantial activity in relapsed gliomas.