Enzastaurin (ENZ) before and concomitant with radiation therapy (RTX), followed by ENZ maintenance therapy in patients with newly diagnosed glioblastoma (GBM) without hypermethylation of the O6-methylguanyl DNA-methyltransferase (MGMT) promoter: A multicenter, open-label, uncontrolled phase II study

e13038 Background: There is an unmet need to improve efficacy outcome for GBM patients without hypermethylation of the MGMT promoter. Preclinical data indicated a potential benefit of ENZ, an oral serine/threonine kinase inhibitor, together with RTX (Tabatabai et al; Ann Neurol 61: 2007). In a run-in phase of this phase II study the feasibility of once or twice daily ENZ dosing was evaluated. The split dose results in higher exposure. The results of the run-in phase are presented. Methods: Patients (pts) with newly diagnosed supratentorial GBM were entered. The first regimen administered once daily ENZ (500 mg QD) before and concomitant with standard radiotherapy at a dose of 60 Gy (2 Gy, 5 days a week). As no dose-limiting toxicities occurred in the first 3 pts, another 6 pts were enrolled into the second regimen, twice daily ENZ (250 mg BID) with RTX. ENZ is given until progression afterward. Results: Between 10/07 and 07/08 a total of 9 pts were enrolled. Mean treatment duration was 9.3 weeks for ENZ, ...