Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castration-resistant prostate cancer: implications for prior therapy in clinical trials

Urologic Oncology
Gregory R PondG Sonpavde

Abstract

Abiraterone acetate (AA) is a CYP17 inhibitor of androgen synthesis approved for use following docetaxel for metastatic castration-resistant prostate cancer (mCRPC); evaluation in the pre-docetaxel setting is ongoing. Given that the reported efficacy of AA is lower following docetaxel vs. pre-docetaxel, the potential exists for cross resistance given docetaxel's partly androgen receptor targeting activity. The efficacy of docetaxel following ketoconazole (KC), a weaker and nonspecific inhibitor of CYP17, may provide some insights into this potential interaction. We retrospectively evaluated the efficacy of every 3-week docetaxel with prednisone (DP) in mCRPC previously exposed to KC compared to KC-naive patients. A randomized phase II trial of men with mCRPC treated with DP + AT-101 (bcl-2 inhibitor) vs. DP plus placebo was analyzed. Both arms were combined for analysis as no significant differences were seen. Overall survival (OS), progression-free survival (PFS), objective response (ORR), pain, and prostate-specific antigen (PSA) response rates were estimated with and without prior KC. Cox proportional hazards regression models were used to estimate the effect of covariates on OS. Of 220 evaluable men, 40 (18.2%) received pri...Continue Reading

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Jan 18, 2014·Asian Journal of Andrology·Michael T Schweizer, Emmanuel S Antonarakis
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