Ketoconazole is an imidazole antifungal agent that inhibits adrenal androgen synthesis, although it does have a direct cytotoxic effect on prostatic cancer cells in vitro. Ketoconazole is less specific than abiraterone. In a phase III trial conducted by the Cancer and Leukemia Group B (CALGB 9583), a subgroup of patients who had progressed on androgen deprivation therapy were assigned to anti-androgen withdrawal alone.1Upon PSA progression, patients were treated with ketoconazole plus hydrocortisone. Thirty-two percent had a PSA response, and 7% with measurable disease had an objective response.

A retrospective study of 32 patients given ketoconazole at 200 mg thrice daily at 2 tertiary cancer centres in Singapore demonstrated a PSA response rate (defined as at least 50% decrease in PSA level from baseline) of 38% and a median duration of response of 6.75 months.16The median time to reach PSA nadir was 3.5 months (range, 1.5 to 11 months).