A Meta-Analysis and Indirect Comparison of Endothelin A Receptor Antagonist for Castration-Resistant Prostate Cancer.

BACKGROUND - Endothelin A (ET-A) receptor antagonists including zibotentan and atrasentan, have been suggested as a treatment for castration-resistant prostate cancer (CRPC). Our aim was to conduct a meta-analysis and indirect comparison to assess the efficacy and safety of ET-A receptor antagonists for treatment of CRPC.

METHODS - We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science from inception to November 2014 to identify randomized controlled trials (RCTs) which assessed ET-A receptor antagonists for treatment of CRPC. Meta-analysis was conducted by STATA version 12.0 software.

RESULTS - Eight RCTs were identified, involving 6,065 patients. The results of direct comparison showed that compared with placebo, there was no statistically significant difference in the improvement of progression-free survival (PFS), overall survival (OS), time to disease progression (TTP), and total adverse events (AEs) with ET-A receptor antagonist treatment for CRPC. The results of ET-A receptor antagonists plus docetaxel versus docetaxel alone were similar. The indirect comparisons showed that there were no significant differences between zibotentan plus docetaxel versus atrasentan plus docetaxel when compared with docetaxel alone or zibotentan versus atrasenta compared with placebo in the improvement of PFS, OS, TTP, and total adverse events.

CONCLUSIONS - There were no significant benefits for ET-A receptor antagonists with or without docetaxel in the improvement of PFS, OS, TTP, and overall AEs. And there were no significant differences between zibotentan and atrasentan. Single-agent docetaxel should remain as one of the standard treatments.

PLoS One. 2015 Jul 20;10(7):e0133803. doi: 10.1371/journal.pone.0133803. eCollection 2015.

Qi P1, Chen M2, Zhang LX3, Song RX4, He ZH5, Wang ZP4.

1 Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Department of Clinical Laboratory, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
2 Department of Urology, GanSu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China.
3 Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
4 Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Key Laboratory of Urological Diseases in Gansu Province, Lanzhou 730030, China.
5 Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou 730030, China.

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