ESSAY

The role of ketoconazole in current prostate cancer care

Abstract

Ketoconazole is a nonselective steroid 17α-hydroxylase/17,20 lyase (CYP17A1) inhibitor that has been used, off-label, as a second-line therapy for castration-resistant prostate cancer (CRPC). The drug has shown clinical efficacy without survival benefit. Despite not improving survival, ketoconazole has beneficial characteristics, such as its low cost, a relatively favourable toxicity profile compared with chemotherapy, and its efficacy both before and after chemotherapy. The approval of several new, highly effective treatments, including abiraterone acetate, enzalutamide, and apalutamide, warrants re-evaluation of the role of ketoconazole and other classic agents in achieving the optimal timing and sequencing of available agents to prolong survival and maintain patients’ quality of life. In the current CRPC treatment landscape, we believe that ketoconazole can be considered in patients with nonmetastatic CRPC and in those with metastatic CRPC who do not respond to, tolerate, or have access to chemotherapy and other standard therapeutic options.

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Fig. 1: The activity of ketoconazole on the steroid synthesis pathway in the adrenal gland and testis.
Fig. 2: Intratumoral androgen synthesis leading to castration resistance and the role of CYP17A1 inhibition.
Fig. 3: The role of ketoconazole in current CRPC treatment scenarios.

Figure adapted from ref.87, BMJ.

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Nature Reviews Urology thanks M. Carducci and W. Figg for their contribution to the peer review of this work.

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V.P. and B.L. researched data and made substantial contributions to discussion of the content of the article. All authors wrote and reviewed and/or edited the manuscript before submission.

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Patel, V., Liaw, B. & Oh, W. The role of ketoconazole in current prostate cancer care. Nat Rev Urol 15, 643–651 (2018). https://doi.org/10.1038/s41585-018-0077-y

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