Temozolomide may prolong survival in glioblastoma patients

Adding the alkylating agent temozolomide to radiotherapy for the treatment of glioblastoma extends survival, according to the results of a phase III trial. Moreover, a tumor-specific marker can be used to predict which patients are most likely to respond to temozolomide treatment, the results of another study indicate.

Dr. Roger Stupp, at Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, randomized patients with newly diagnosed glioblastoma to standard focal radiotherapy alone (n = 286) or radiotherapy plus temozolomide (n = 287). Eight-four percent of the patients underwent surgical debulking of the tumor.Temozolomide was administered during radiation therapy and in six cycles of adjuvant therapy following radiation. Salvage therapy in the event of disease progression was instituted at physician discretion.Median survival was 12.1 months in the radiation-only group and 14.6 months in the temozolomide group. Two-year survival rates were 10.4% and 26.5%, respectively, “a clinically meaningful increase,” the authors report.Grade 3 or 4 hematologic toxicities were observed in 7% of those treated with temozolomide. Standard antiemetic agents were used to control nausea.In the second study, lead investigator Dr. Monika E. Hegi, at University Hospital in Lausanne, and colleagues, found that methylation of the MGMT (O6-methylguanine-DNA methyltransferase) promoter, which results in gene silencing, was associated with a survival benefit in glioblastoma patients who received temozolomide.The methylation status of the MGMT promoter, according to methylation-specific polymerase chain reaction analysis, was determined in specimens from 206 tumors.”The median overall survival among patients with methylation was 18.2 months compared with 12.2 months among those without methylation,” the researchers report. The longest median overall survival was 21.7 months in patients with promoter methylation who were treated with temozolomide.Temozolomide had little effect on patients whose tumors were not methylated at the MGMT promoter.The findings of both studies are reported in the March 10th issue of The New England Journal of Medicine.In an accompanying editorial, Dr. Lisa M. DeAngelis, at Memorial Sloan-Kettering Cancer Center in New York, notes that testing for MGMT promoter methylation is not an easy technique, even in experienced hands, and is not widely available.”Therefore, it seems reasonable to administer temozolomide with radiotherapy to all patients with newly diagnosed glioblastoma,” she writes.(Source: N Engl J Med 2005;352:987-1003,1036-1037: Reuters Health: Oncolink: March 2005.)