this phase iii open label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma who grade 4 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 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 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.