Efficacy
The evidence supporting this protocol is provided by the phase III multicentre international randomised trial (EORTC 22981/26981) involving 573 patients (18-70 years old) comparing radiation therapy alone with radiation therapy plus temozolomide (TMZ), concomitant and adjuvant, in patients with newly diagnosed glioblastoma.rr
- Between 2000 and 2002, 286 patients were randomised to receive radiation therapy alone (60 Gy in 30 fractions) and 287 patients were randomised to receive radiation therapy (60 Gy in 30 fractions) and continuous daily TMZ (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy) followed by six cycles of adjuvant TMZ (150 to 200 mg 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 radiation therapy plus TMZ group versus 12.1 months in the radiation therapy alone group (HR = 0.63, 95% CI:0.52-0.75, p <0.001).
- The 2-year overall survival was 26.5% in the radiation therapy plus TMZ group versus 10.4% in the radiation therapy alone group. 2-year progression free survival was 11.2% in the radiation therapy plus TMZ group and 1.8% in the radiation therapy alone group.
- The updated 5-year results showed 5-year survival of 9.8% versus 1.9% (figure 1).r
Figure 1: Kaplan-Meier estimate of overall survival by treatment group
© Lancet Oncolr
Athanassiou et al. conducted a phase III trial including 131 patients.r They reported a median survival of 13.4 months with combined modality (concurrent and adjuvant TMZ) compared to 7.7 months with radiation therapy alone.
Regarding the benefit of radiation therapy alone, Laperriere et al. conducted a systematic review which included 6 randomised controlled trials comparing conventional radiation therapy with no radiation therapy.r Patient groups included grade 3 and 4 gliomas. Doses ranged from 50-60 Gy. Laperriere et al. reported a survival benefit with post-operative radiation therapy (RR = 0.81, 95% CI:0.74-0.88, p <0.00001).