TY - JOUR
T1 - Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study
T2 - 5-year analysis of the EORTC-NCIC trial
AU - Stupp, Roger
AU - Hegi, Monika E.
AU - Mason, Warren P.
AU - van den Bent, Martin J.
AU - Taphoorn, Martin JB
AU - Janzer, Robert C.
AU - Ludwin, Samuel K.
AU - Allgeier, Anouk
AU - Fisher, Barbara
AU - Belanger, Karl
AU - Hau, Peter
AU - Brandes, Alba A.
AU - Gijtenbeek, Johanna
AU - Marosi, Christine
AU - Vecht, Charles J.
AU - Mokhtari, Karima
AU - Wesseling, Pieter
AU - Villa, Salvador
AU - Eisenhauer, Elizabeth
AU - Gorlia, Thierry
AU - Weller, Michael
AU - Lacombe, Denis
AU - Cairncross, J. Gregory
AU - Mirimanoff, René Olivier
N1 - Funding Information:
Frances Godson provided editorial assistance in the preparation of the report. MGMT testing was done by Annie-Claire Diserens and supported by grants from the Nélia and Amadeo Barletta Foundation, the EORTC Translational Reseach Fund 2002, and the Jacqueline Seroussi Memorial Foundation for Cancer Research. We thank all patients who participated in the study and acknowledge the great contributions of physicians and nurses taking care of the patients. The trial was supported by an unrestricted educational grant and drug supply from Schering-Plough (Kenilworth, NJ, USA). The study was developed and organised by the EORTC Data Centre, the EORTC Brain Tumour and Radiation Oncology Groups, and NCIC Clinical Trials Group; members of the Swiss Cooperative Group for Clinical Cancer Research (SAKK) and Tasmanian Radiation Oncology Group (TROG) also recruited to the study. A full list of the 85 participating institutions and investigators can be found online ( webappendix ).
PY - 2009/5
Y1 - 2009/5
N2 - Background: 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. Methods: 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 NCT00006353. Findings: 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 chemotherapy. Interpretation: 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 temozolomide. Funding: EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.
AB - Background: 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. Methods: 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 NCT00006353. Findings: 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 chemotherapy. Interpretation: 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 temozolomide. Funding: EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.
UR - http://www.scopus.com/inward/record.url?scp=65349121788&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(09)70025-7
DO - 10.1016/S1470-2045(09)70025-7
M3 - Article
C2 - 19269895
AN - SCOPUS:65349121788
SN - 1470-2045
VL - 10
SP - 459
EP - 466
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 5
ER -