Whole-brain irradiation with concomitant daily fixed-dose Temozolomide for brain metastases treatment: A randomised phase II trial

Background and purpose: This randomised phase II study evaluated the use of Temozolomide (TMZ) concomitant with 30 Gray (Gy) of Whole-brain irradiation (WBI) for 2 weeks without adjuvant TMZ vs. WBI alone in patients with Brain metastases (BM) from solid tumours. Materials and methods: Fifty-five patients were randomised into the following groups: 28 patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with once-daily 200 mg TMZ on Mondays, Wednesdays, and Fridays, and 300 mg TMZ on Tuesdays and Thursdays (TMZ plus WBI arm). Twenty-seven patients received the same schedule of WBI alone (control arm). Results: The objective response (OR) was 78.6% for the TMZ plus WBI arm, (95% confidence interval [CI], 63.4–93.8%) and 48.1% (29.3–66.9%) for the control arm (p = 0.019). Median Progression-free survival (PFS) of BM was 11.8 months (CI, 4.7–8.9 months) and 5.6 months (4.9–6.2 months) for the TMZ plus WBI and control arms, respectively, (Hazard ratio [HR], 0.24; CI, 0.09–0.65; p = 0.005). Overall survival (OS) of 8.0 Months for the TMZ plus WBI arm and 8.1 months for the control arm, were not significantly different. Conclusion: A daily fixed dose of TMZ during WBI without adjuvant TMZ was well tolerated and significantly improved local control of BM compared with WBI alone. These findings require confirmation in a phase III trial (ClinicalTrials.gov number, (NCT01015534)).