The evidence supporting this protocol is provided by the phase III multicenter international randomised trial (EORTC 22981/26981) involving 573 patients (18-70 years old) comparing radiotherapy alone with radiotherapy-plus-temozolomide concomitant and adjuvant in patients with newly diagnosed glioblastoma.r
- Between 2000 and 2002, 286 patients were randomized to receive radiotherapy alone (60Gy in 30#) and 287 patients were randomized to receive radiotherapy (60Gy in 30#) and continuous daily temozolomide (75mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy ) followed by six cycles of adjuvant temozolomide (150 to 200mg per square meter for 5 days during each 28-day cycle).
- The primary end point was overall survival and secondary end points were progression-free survival, safety and quality of life.
- After a median follow up of 28 months, the median survival was 14.6 months in the radiotherapy-plus-temozolomide group vs 12.1 months in the RT alone group (HR= 0.63, CI 95% 0.52-0.75; p<0.001).
- The 2 year overall survival was 26.5% in the radiotherapy-plus-temozolomide group vs 10.4% RT alone group and 2 year progression free survival was 11.2% in the radiotherapy-plus-temozolomide group and 1.8% in the RT alone group.
- The updated 5 year results (shown in Figure 1 below), showed 5 year survivals of 9.8% versus 1.9%.r
Figure 1: Kaplan-Meier estimate of overall survival by treatment groupr
© Lancet Oncol.r
Athanassiou et al. (2005) conducted a phase III trial including 131 patients. They reported a median survival of 13.4 months with combined modality (with concurrent and adjuvant temozolomide) compared to 7.7 months with RT alone.r
Regarding the benefit of radiotherapy alone, Laperriere et al. (2002) conducted a systematic review which included 6 randomised controlled trials comparing conventional radiation with no radiation. Patient groups included grade 3 and 4 gliomas. Doses ranged from 50-60Gy. Laperriere et al (2002) reported a survival benefit with post-op RT (RR 0.81, 95% CT 0.74-0.88, P<0.00001).r