BACKGROUND: Endothelin-1 and the endothelin A (ETA ) receptor have been implicated in prostate cancer progression in bone.
This study aimed to determine whether the specific ETAreceptor antagonist, zibotentan, prolonged overall survival (OS) in patients with castration-resistant prostate cancer and bone metastases who were pain-free or mildly symptomatic for pain.
METHODS:Patients were randomized 1:1 to zibotentan 10 mg/day or placebo, plus standard prostate cancer treatment. The primary endpoint was OS. Secondary endpoints included times to pain progression, chemotherapy use, new bone metastases, and safety. Efficacy endpoints were analyzed using a log-rank test.
RESULTS:A total of 594 patients were randomized (zibotentan, n = 299; placebo, n = 295). Median OS was 24.5 months in zibotentan-treated patients versus 22.5 months for placebo, but the difference did not reach statistical significance (hazard ratio, 0.87; 95.2% confidence interval, 0.69-1.10; P = .240). No statistically significant differences were observed for any secondary efficacy endpoints. Peripheral edema (44%) and headache (31%) were the most commonly reported adverse events in the zibotentan group. Cardiac failure events were higher in the zibotentan group than placebo (any grade, 5.7% and 1.7%; Common Terminology Criteria for Adverse Events grade ≥3, 3.0% and 1.0%, respectively); these were manageable and reversible.
CONCLUSIONS: In this large, randomized, placebo-controlled phase 3 trial, treatment with zibotentan 10 mg/day did not lead to a statistically significant improvement in OS in this patient population. Zibotentan had an acceptable safety profile.
Written by:
Nelson JB, Fizazi K, Miller K, Higano C, Moul JW, Akaza H, Morris T, McIntosh S, Pemberton K, Gleave M. Are you the author?
University of Pittsburgh, Pittsburgh, Pennsylvania.
Reference: Cancer. 2012 Jul 11. Epub ahead of print.
doi: 10.1002/cncr.27674
PubMed Abstract
PMID: 22786751
UroToday.com Prostate Cancer Section
