PURPOSE: This phase III open-label study compared the efficacy and safety of 
enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 
4).
PATIENTS AND METHODS: Patients were randomly assigned 2:1 to receive 6-week 
cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 
to 130 mg/m(2), day 1). Assuming a 45% improvement in progression-free survival 
(PFS), 397 patients were required to provide 80% power to achieve statistical 
significance at a one-sided level of .025.
RESULTS: Enrollment was terminated at 266 patients (enzastaurin, n = 174; 
lomustine, n = 92) after a planned interim analysis for futility. Patient 
characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard 
ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR 
= 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ 
significantly between enzastaurin and lomustine, respectively. Stable disease 
occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% 
and 4.3% of patients, respectively. Time to deterioration of physical and 
functional well-being and symptoms did not differ between arms (HR = 1.12; P = 
.54). Four patients discontinued enzastaurin because of drug-related serious 
adverse events (AEs). Eleven patients treated with enzastaurin died on study 
(four because of AEs; one was drug-related). All four deaths that occurred in 
patients receiving lomustine were disease-related. Grade 3 to 4 hematologic 
toxicities were significantly higher with lomustine (46 events) than with 
enzastaurin (one event; P < or = .001).
CONCLUSION: Enzastaurin was well tolerated and had a better hematologic toxicity 
profile but did not have superior efficacy compared with lomustine in patients 
with recurrent glioblastoma.