This open-label, single-arm, phase II study combined enzastaurin with 
temozolomide plus radiation therapy (RT) to treat glioblastoma multiforme (GBM) 
and gliosarcoma. Adults with newly diagnosed disease and Karnofsky performance 
status (KPS) ≥ 60 were enrolled. Treatment was started within 5 weeks after 
surgical diagnosis. RT consisted of 60 Gy over 6 weeks. Temozolomide was given 
at 75 mg/m(2) daily during RT and then adjuvantly at 200 mg/m(2) daily for 5 
days, followed by a 23-day break. Enzastaurin was given once daily during RT and 
in the adjuvant period at 250 mg/day. Cycles were 28 days. The primary end point 
was overall survival (OS). Progression-free survival (PFS), toxicity, and 
correlations between efficacy and molecular markers analyzed from tumor tissue 
samples were also evaluated. A prospectively planned analysis compared OS and 
PFS of the current trial with outcomes from 3 historical phase II trials that 
combined novel agents with temozolomide plus RT in patients with GBM or 
gliosarcoma. Sixty-six patients were enrolled. The treatment regimen was well 
tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the 
current trial were comparable to those from a prior phase II study using 
erlotinib and were significantly better than those from 2 other previous studies 
that used thalidomide or cis-retinoic acid, all in combination with temozolomide 
plus RT. A positive correlation between O-6-methylguanine-DNA methyltransferase 
promoter methylation and OS was observed. Adjusting for age and KPS, no other 
biomarker was associated with survival outcome. Correlation of relevant 
biomarkers with OS may be useful in future trials.