Temozolomide in the treatment of recurrent malignant glioma.

Background: Options for chemotherapy at the time of recurrence in patients with malignant glioma are limited. The authors describe the efficacy and safety results of their institution's open-label, compassionate-use protocol of temozolomide for patients with recurrent malignant glioma.

Methods: Patients with recurrent malignant glioma at any time during recurrence were treated with oral temozolomide at a dose of 150 mg/m2 per day on a 5-day schedule every 28 days. If this dose was tolerated, then escalation to 200 mg/m2 was allowed. Clinical evaluations and assessments of tumor response were performed every 2 months. All patients or their surrogates signed approved Institutional Review Board consent forms.

Results: Among 213 patients who were treated, 33% had Grade 3 tumors, and 67% had Grade 4 tumors. The overall objective response rate was 16% in both of these patient groups; and an additional 51% and 30% of patients with Grade 3 and Grade 4 tumors, respectively, had stable disease as their best response. The 6-month progression-free survival rates were 41% and 18% for patients with Grade 3 and Grade 4 tumors, respectively. The median survival was 49 weeks for patients with Grade 3 tumors and 32 weeks for patients with Grade 4 tumors. The major toxicity was hematologic toxicity. In multivariate analysis, the Karnofsky performance score was a significant predictor of survival for patients with Grade 4 tumors.

Conclusions: Temozolomide was well tolerated in patients with recurrent malignant glioma and had modest efficacy, even at the time of multiple recurrences.