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A North Central Cancer Treatment Group phase II trial of topotecan in relapsed gliomas
P A Burch1, A M Bernath, T L Cascino
1Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Abstract:
Current systemic treatment options for patients with relapsed gliomas are limited. The topoisomerase I inhibitor topotecan has demonstrated broad antitumor activity in both preclinical studies as well as a number of phase I and II trials in humans. Studies in primates have shown good cerebrospinal fluid levels of topotecan following systemic administration. We therefore performed this phase II trial in patients who developed evidence of progressive glioma after definitive radiation therapy. Patients were treated with 1.5 mg/m2 intravenously daily for 5 consecutive days repeated every three weeks. For patients who had received prior nitrosourea-containing chemotherapy, the starting dose was 1.25 mg/m2. Thirty-three patients were entered on this study. All patients were eligible and evaluable for both response and toxicity. Seven patients experienced grade 4 leukopenia with 2 of these patients dying of infection-related complications. Six of these seven patients were not taking anticonvulsants during treatment. Nine patients developed grade 3-4 thrombocytopenia, seven of whom were not taking anticonvulsants. Nonhematologic side effects were infrequent and manageable. One patient experienced a partial response to this treatment for an overall response rate 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 this dose and schedule showed no substantial activity in relapsed gliomas.
Insights
Topotecan, a topoisomerase I inhibitor, showed limited efficacy in treating relapsed gliomas. This phase II trial found minimal antitumor activity and significant toxicity, suggesting it is not a viable treatment option for these patients.
Area of Science:
- Neuro-oncology
- Medical oncology
- Pharmacology
Background:
- Limited systemic treatment options exist for patients with relapsed gliomas.
- Topotecan, a topoisomerase I inhibitor, has shown preclinical and early clinical antitumor activity.
- Cerebrospinal fluid penetration of topotecan has been demonstrated in primate studies.
Purpose of the Study:
- To evaluate the efficacy and toxicity of topotecan in patients with relapsed gliomas after radiation therapy.
- To determine the overall response rate, time to progression, and survival in this patient population.
Main Methods:
- A phase II clinical trial was conducted.
- Patients received topotecan intravenously at 1.5 mg/m2 daily for 5 consecutive days every three weeks (1.25 mg/m2 for prior nitrosourea exposure).
- Response and toxicity were assessed in 33 evaluable patients.
Main Results:
- An overall response rate of 3% was observed.
- Median time to progression was 14.9 weeks, and median survival was 19.9 weeks.
- Significant toxicities included grade 4 leukopenia (7 patients, 2 deaths) and grade 3-4 thrombocytopenia (9 patients), particularly in those not taking anticonvulsants.
Conclusions:
- Topotecan at the tested dose and schedule demonstrated no substantial activity in relapsed gliomas.
- The observed toxicities, including life-threatening infections, raise concerns about its safety profile in this context.