Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients

Background:ketoconazole is a well-known cyp17-targeted systemic treatment for castration-resistant prostate cancer (crpc). however, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200–300 mg three times daily) had psa response rate (>50% decline) of 21–62%. we hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the crpc post-chemotherapy state.methods:men with crpc and performance status 0–3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg po qam and 10 mg po qpm) until disease progression. primary endpoint was psa response rate (>50% reduction from baseline) where a rate of 25% was to be considered promising for further study (versus a null rate of <5%); 25 patients were required. secondary endpoints included psa response >30% from baseline, progression-free survival (pfs), duration of stable disease and evaluation of adverse events (aes).results:thirty patients were accrued with median age of 72 years (range 55–86) and median pre-treatment psa of 73 ng ml−1 (range 7–11,420). twenty-nine patients were evaluable for response and toxicity. psa response (>50% reduction) was seen in 48% of patients; psa response (>30% reduction) was seen in 59%. median pfs was 138 days; median duration of stable disease was 123 days. twelve patients experienced grade 3 or 4 aes. of the 17 grade 3 aes, only 3 were attributed to treatment. none of the two grade 4 aes were considered related to treatment.conclusions:in docetaxel pre-treated crpc patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. psa response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. a prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy.