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 adjuvanttemozolomide 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 theradiotherapy 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.
RCT Entities:
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.
Authors: Georges Noel; Aymeri Huchet; Loic Feuvret; Jean Philippe Maire; Pierre Verrelle; Emilie Le Rhun; Maud Aumont; François Thillays; Marie Pierre Sunyach; Chantal Henzen; Fernand Missohou; Renaud de Crevoisier; Pierre Yves Bondiau; Philippe Collin; Xavier Durando; Gilles Truc; Christine Kerr; Valérie Bernier; Jean-Baptiste Clavier; David Atlani; Anne D'Hombres; Sandrine Vinchon-Petit; Jean Léon Lagrange; Luc Taillandier Journal: J Neurooncol Date: 2012-06-02 Impact factor: 4.130
Authors: Nathalie Gaspar; Swee Y Sharp; Suzanne A Eccles; Sharon Gowan; Sergey Popov; Chris Jones; Andrew Pearson; Gilles Vassal; Paul Workman Journal: Mol Cancer Ther Date: 2010-05 Impact factor: 6.261
Authors: Muhammad M Abd-El-Barr; Kevin T Huang; Ziev B Moses; J Bryan Iorgulescu; John H Chi Journal: Neuro Oncol Date: 2018-05-18 Impact factor: 12.300
Authors: Xiuxing Wang; Zhi Huang; Qiulian Wu; Briana C Prager; Stephen C Mack; Kailin Yang; Leo J Y Kim; Ryan C Gimple; Yu Shi; Sisi Lai; Qi Xie; Tyler E Miller; Christopher G Hubert; Anne Song; Zhen Dong; Wenchao Zhou; Xiaoguang Fang; Zhe Zhu; Vaidehi Mahadev; Shideng Bao; Jeremy N Rich Journal: Cancer Res Date: 2017-07-20 Impact factor: 12.701
Authors: David Svilar; Madhu Dyavaiah; Ashley R Brown; Jiang-bo Tang; Jianfeng Li; Peter R McDonald; Tong Ying Shun; Andrea Braganza; Xiao-hong Wang; Salony Maniar; Claudette M St Croix; John S Lazo; Ian F Pollack; Thomas J Begley; Robert W Sobol Journal: Mol Cancer Res Date: 2012-10-04 Impact factor: 5.852