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 pf 150 mg/m(2) per day on a 5-day schedule every 28 days. If this dose was tolerated, then escalation to 200 mg/m(2) 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.