In 2004, a randomised phase III trial by the European Organisation for Research and
Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials
Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma
treated with concomitant and adjuvant temozolomide and radiotherapy. We report the
final results with a median follow-up of more than 5 years.
Adult patients with newly diagnosed glioblastoma were randomly assigned to receive
either standard radiotherapy or identical radiotherapy with concomitant temozolomide
followed by up to six cycles of adjuvant temozolomide. The methylation status of the
methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from
the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses
were by intention to treat. This trial is registered with Clinicaltrials.gov, number
Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment.
278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in
the combined-treatment group died during 5 years of follow-up. Overall survival was
27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4)
at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8),
4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard
ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in
all clinical prognostic subgroups, including patients aged 60-70 years. Methylation
of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide
Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up.
A few patients in favourable prognostic categories survive longer than 5 years. MGMT
methylation status identifies patients most likely to benefit from the addition of
EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.