LOS ANGELES—With the combination of radiation therapy and temozolomide(Drug information on temozolomide) (Temodar), some patients with glioblastoma multiforme are now surviving more than 4 years, according to updated results from a randomized phase III trial presented at ASTRO's 49th annual meeting (abstract 3).
"In 2005, our group demonstrated for the first time that concomitant treatment with temozolomide and radiation [plus adjuvant temozolomide] improved median and 2-year survival, compared with radiation alone, in glioblastoma," said lead author René-Olivier Mirimanoff, MD, of the University of Lausanne Medical Center, CHUV, in Switzerland (N Engl J Med 352:987-996, 2005). "However, it was not known, of course, at that time whether the survival advantage would remain with longer follow-up."
The joint EORTC-NCIC trial enrolled adults with newly diagnosed, histologically proven glioblastoma who had a good performance status, had not previously received chemotherapy or radiation therapy, and were no more than 6 weeks out from biopsy or resection.
Patients received 6 weeks of radiation therapy to a total dose of 60 Gy, either alone or with added concomitant temozolomide (75 mg/m2 daily) and adjuvant temozolomide (150 to 200 mg/m2 daily on days 1-5 of a 28-day cycle, for six cycles).
For each patient, the investigators determined recursive partitioning analysis (RPA) class—III (best prognostic features), IV (intermediate), or V (worst)—and methylation status of the promoter of MGMT, a gene that codes for a repair enzyme. Methylation silences the enzyme, increasing susceptibility to chemotherapy and likely to radiation therapy, Dr. Mirimanoff explained.
In the updated analysis, the median follow-up was 61 months among the 573 patients. "With time, the advantage conferred by the addition of temozolomide to radiation vs radiation alone remained highly statistically significant at 2, 3, and 4 years," he said.
The 4-year rate of overall survival (the trial's primary endpoint) was 12.1% in the radiation/temozolomide group, compared with 3.0% in the radiation-only group (HR 0.63, P < .0001), he reported.
