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Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma.


ABSTRACT: 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.

SUBMITTER: Wick W 

PROVIDER: S-EPMC2834468 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma.

Wick Wolfgang W   Puduvalli Vinay K VK   Chamberlain Marc C MC   van den Bent Martin J MJ   Carpentier Antoine F AF   Cher Lawrence M LM   Mason Warren W   Weller Michael M   Hong Shengyan S   Musib Luna L   Liepa Astra M AM   Thornton Donald E DE   Fine Howard A HA  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20100201 7


<h4>Purpose</h4>This phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4).<h4>Patients and methods</h4>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  ...[more]

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