Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study.

BACKGROUND AND PURPOSE: The common treatment in patients with newly diagnosed glioblastoma multiforme is the ultimately radical surgical removal of the tumour combined with radiotherapy. This study compared safety and efficacy of radiotherapy alone with radiotherapy combined with temozolomide (TMZ) given before, during, and after radiotherapy.

MATERIAL AND METHODS: The patients operated on for glioblastoma multiforme during the first 21 postoperative days were randomly assigned to the group treated with radiotherapy alone (involved-field radiotherapy in 2 Gy fractions daily five times a week up to the total of 60 Gy over 6 weeks of treatment) or to the group treated with radiotherapy and TMZ, initially in the dose of 200 mg/m² during 5 postoperative days and after 23 days followed by 75 mg/m2 of body surface area daily, 7 days a week (from the first to the last day of radiotherapy). On completion of radiotherapy, five complementary courses of TMZ were introduced (150-200 mg/m² for 5 days, repeated every 28 days). The primary outcome measure was overall survival.

RESULTS: Fifty-eight patients from 3 centres were included in the study. The mean age of patients was 55 years and all the patients underwent a surgical procedure of glioblastoma removal. The mean overall survival in the group treated with TMZ was 16.0 months, whereas in the group with radiotherapy alone the overall survival reached 12.5 months. 24-month survival reached 23% in patients treated with TMZ and 6.7% in those who received radiotherapy only. Haematological complications of third or fourth degree were present in 10% of patients treated with radiotherapy and TMZ.

CONCLUSIONS: The introduction of TMZ before, during and after radiotherapy for newly diagnosed glioblastoma multiforme gives clinically and statistically significant improvement of survival with unremarkably increased toxicity of the treatment.