Irinotecan treatment for recurrent malignant glioma using an every-3-week regimen.

This phase II study was designed to evaluate the safety, tolerability, and efficacy of irinotecan (CPT-11) in the treatment of adults with malignant glioma. Patients with progressive or recurrent malignant gliomas were enrolled. CPT-11 was administered as a 90-minute intravenous infusion at a dose of 300 mg/m(2) once a week every 3 weeks. After 2 treatments, doses were increased to 350 mg/m(2) in those patients without grade III/IV toxicities. Dose modifications were made for toxicities. All 14 patients who enrolled (11 males and 3 females) were treated with CPT-11 and were assessable for survival, response, and toxicity. The majority of patients (86%) had prior surgery. Two patients had a confirmed partial response and 2 patients (14%) had stable disease. Median survival was 24 weeks. Median time to tumor progression was 6 weeks. The primary hematologic toxicity was grade III/IV neutropenia, which was observed in 14% of patients. Infrequent grade III/IV nonhematologic toxicity was observed, possibly because of the concomitant use of anticonvulsants, which may have altered pharmacokinetics. These results suggest that CPT-11 has activity against recurrent malignant glioma using a dosing regimen of 300 mg/m(2) every 3 weeks showing limited toxicity. The concurrent use of anticonvulsant medications may have played a role in altering pharmacokinetics and thus the maximum tolerated dose in this patient population.