BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is us ually rapidly fatal. The current standard of care for newly diagnosed glioblasto ma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy p lus temozolomide, given concomitantly with and after radiotherapy, in terms of e fficacy and safety. METHODS: Patients with newly diagnosed, histologically confi rmed glioblastoma were randomly assigned to receive radiotherapy alone (fraction ated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 we eks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (7 5 mg per square meter of body-surface area per day, 7 days per week from the fi rst to the last day of radiotherapy), followed by six cycles of adjuvant temozol omide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 8 5 centers underwent randomization. The median age was 56 years, and 84 percent o f patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12. 1 months with radiotherapy alone. The unadjusted hazard ratio for death in the r adiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P < 0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiother apy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologie toxic effects in 7 percent of patients. CONCLUSIONS: T he addition of temozolomide to radiotherapy for newly diagnosed glioblastoma res ulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity. BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is us ually rapidly fatal. The current standard of care for newly diagnosed glioblasto ma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with METHODS: Patients with newly diagnosed, histologically confi rmed glioblastoma were randomly assigned to receive radiotherapy alone (fraction ated focal irradiation in daily fractions of 2 Gy given in radiofrequency ab lus temozolomide, given concomitantly with and after radiotherapy, in terms of e fficacy and safety. 5 days per week for 6 we eks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (7 5 mg per square meter of body-surface area per day, 7 days per week from the fi rst to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESUL TS: A total of 573 patients from 8 5 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12. 1 months with radiotherapy alone. The unadjusted hazard ratio for death in the adiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P <0.001 by the log-rank test). The two -year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiother apy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologie toxic effects in 7 percent of patients. CONCLUSIONS: T he addition of temozolomide to radiotherapy for newly diagnosed glioblastoma res ulted in a clinically meaningful and minor significant survival benefit with minimal additional toxicity.