A North Central Cancer Treatment Group Phase II Trial of Topotecan in Relapsed Gliomas

Current systemic treatment options for patientswith relapsed gliomas are limited. Thetopoisomerase I inhibitor topotecan has demonstrated broadantitumor activity in both preclinicalstudies as well as a number of phase I and II trials in humans.Studies in primates have shown goodcerebrospinal fluid levels of topotecan following systemicadministration. We therefore performed this phase II trial in patients who developed evidence of progressive glioma after definitive radiation therapy. Patients were treated with 1.5mg/m2 intravenously daily for 5 consecutive days repeatedevery three weeks. For patients who had received priornitrosourea-containing chemotherapy, thestarting dose was 1.25 mg/m2. Thirty-three patients wereentered on this study. All patients wereeligible and evaluable for both response and toxicity. Sevenpatients experienced grade 4 leukopeniawith 2 of these patients dying of infection-relatedcomplications. Six of these seven patients werenot taking anticonvulsants during treatment. Nine patientsdeveloped grade 3-4 thrombocytopenia,seven of whom were not taking anticonvulsants. Nonhematologicside effects were infrequent andmanageable. One patient experienced a partial response to thistreatment for an overall response rateof 3% (95% binomial confidence interval 0.3%-20.4%). The median time to progression was 14.9weeks and median survival 19.9 weeks. Topotecan at this dose andschedule showed no substantial activity in relapsed gliomas.