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...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.展开更多
BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltra nsferase) DNA-repair gene by promoter methylation compromises DNA repair and ha s been associated with longer survival in patients with glio...BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltra nsferase) DNA-repair gene by promoter methylation compromises DNA repair and ha s been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship between MGMT silencing i n the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and ad juvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. RE SULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. I rrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P < 0.001 by the log-rank test; hazard ratio, 0.45; 95 perc ent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a m ethylated MGMT promoter, a survival benefit was observed in patients treated wit h temozolomide and radiotherapy; their median survival was 21.7 months (95 perce nt confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radioth erapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in sur vival between the treatment groups. CONCLUSIONS: Patients with glioblastoma cont aining a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.展开更多
文摘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.
文摘BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltra nsferase) DNA-repair gene by promoter methylation compromises DNA repair and ha s been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship between MGMT silencing i n the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and ad juvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. RE SULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. I rrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P < 0.001 by the log-rank test; hazard ratio, 0.45; 95 perc ent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a m ethylated MGMT promoter, a survival benefit was observed in patients treated wit h temozolomide and radiotherapy; their median survival was 21.7 months (95 perce nt confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radioth erapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in sur vival between the treatment groups. CONCLUSIONS: Patients with glioblastoma cont aining a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.
