We evaluated the efficacy of combination enzastaurin (LY317615) and bevacizumab 
for recurrent malignant gliomas and explored serologic correlates. We enrolled 
81 patients with glioblastomas (GBM, n = 40) and anaplastic gliomas (AG, 
n = 41). Patients received enzastaurin as a loading dose of 1125 mg, followed by 
500 or 875 mg daily for patients on non-enzyme-inducing or enzyme-inducing 
antiepileptics, respectively. Patients received bevacizumab 10 mg/kg 
intravenously biweekly. Clinical evaluations were repeated every 4 weeks. 
Magnetic resonance imaging was obtained at baseline and every 8 weeks from 
treatment onset. Phosphorylated glycogen synthase kinase (GSK)-3 levels from 
peripheral blood mononuclear cells (PBMCs) were checked with each MRI. Median 
overall survival was 7.5 and 12.4 months for glioblastomas and anaplastic glioma 
cohorts, with median progression-free survivals of 2.0 and 4.4 months, 
respectively. Of GBM patients, 3/40 (7.5 %) were not evaluable, while 8/37 
(22 %) had partial or complete response and 20/37 (54 %) had stable disease for 
2+ months. Of the 39 evaluable AG patients, 18 (46 %) had an objective response, 
and 16 (41 %) had stable disease for 2+ months. The most common grade 3+ 
toxicities were lymphopenia (15 %), hypophosphatemia (8.8 %) and thrombotic 
events (7.5 %). Two (2.5 %) GBM patients died suddenly; another death (1.3 %) 
occurred from intractable seizures. Phosphorylated GSK-3 levels from PBMCs did 
not correlate with treatment response. A minimally important improvement in 
health-related quality of life was self-reported in 7-9/24 (29.2-37.5 %). Early 
response based on Levin criteria was significantly associated with significantly 
longer progression free survival for glioblastomas. Enzastaurin (LY317615) in 
combination with bevacizumab for recurrent malignant gliomas is well-tolerated, 
with response and progression-free survival similar to bevacizumab monotherapy.