Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-35465
Wick, W; Puduvalli, V K; Chamberlain, M C; van den Bent, M J; Carpentier, A F; Cher, L M; Mason, W; Weller, M; Hong, S; Musib, L; Liepa, A M; Thornton, D E; Fine, H A (2010). Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. Journal of Clinical Oncology, 28(7):1168-1174.
- Registered users only
View at publisher
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.
57 downloads since deposited on 17 Aug 2010
13 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||17 Aug 2010 11:49|
|Last Modified:||05 Apr 2016 14:13|
|Publisher:||American Society of Clinical Oncology|
|Free access at:||PubMed ID. An embargo period may apply.|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page