Food and Drug Administration drug approval summary: Temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme

On March 15, 2005, the U.S. Food and Drug Administration approved temozolomide (Temodar capsules, Schering-Plough Research Institute) for the treatment of adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment. Five hundred seventy-three glioblastoma multiforme patients were randomized to = 287) or radiotherapy alone (n = 286). Patients receive either temozolomicle + radiotherapy (n mg/m(2)) in the temozolomide + radiotherapy arm received concomitant temozolomide (75 once daily for the duration of radiation therapy (42-49 days). This was followed, 4 weeks later, by six mg/m(2) cycles-of temozolomicle, 150 or 200 daily for 5 days, every 4 weeks. Patients in the control arm received radiotherapy only. In both arms, radiotherapy was delivered as 60 Gy/30 fractions to the tumor site with a 2 to 3 cm margin. Pneumocystis carinii pneumonia prophylaxis was required during temozolomide + radiotherapy treatment and was continued until recovery of lymphocytopenia (Common Toxicity Criteria grade < 1). At disease progression, temozolomide salvage treatment was given to 161 of 282 patients (57%) in the radiotherapy alone arm, and to 62 of 277 patients (22%) in the temozolomide + radiotherapy arm. Patients receiving concomitant and maintenance temozolomide + radiotherapy had significantly improved overall survival, The hazard ratio was 0.63 (95% confidence interval, 0.52-0.75; log-rank, P < 0.0001). Median survival was 14.6 months (temozolomicle + radiotherapy) versus 12.1 months (radiotherapy alone). Adverse events during temozolomide treatment included thrombocytopepia, nausea, vomiting, anorexia, constipation, alopecia, headache, fatigue, and convulsions.