It has always been assumed that Ketoconazole, when used for the treatment of men with metastatic castration resistant prostate cancer (mCRPC), would not be as potent as abiraterone (Zytiga), but there has never been any head to head comparison to demonstrate this assumption! Ketoconazole is a less potent inhibitor of the CYP-17 enzyme, the mode of action of both these drugs, but it as never been shown that this translates into improved survival.

Researchers analyzed the biochemical response rates in 30 post-chemotherapy mCRPC men who were treated with ketoconazole 200 mg TID plus prednisone 5 mg BID at a single center in Denmark. The median age of the men was 66 (range: 58 to 76). Median PSA was 547 ng/ml (65 to 4,241). Median ALP was 159 U/L (51 to 750). The data used for the analysis was derived between 2008 and 2012, where neither abiraterone nor enzalutamide was available in Denmark.

The researchers looked at the percent change in prostate-specific antigen (PSA) and alkaline phosphatase (ALP) from baseline.  They calculated the overall survival from the initiation of ketoconazole therapy.

The researchers also indicated that the median number of prior cancer therapies received by the subject men was five (three to nine). The median time on ketoconazole treatment was 150 days (14 to 648).

They found that a total of 44% of the men had any decline in PSA, whereof 31% experienced a decline of >=50%. At three months, a total of 19 men still received ketoconazole, whereof 26% sustained a PSA decline of >=50% from baseline.

A total of 71% experienced any decline in ALP, whereof 36% experienced a maximum decline of >=50%. At three months, 7 of 19 men (36%) sustained an ALP decline of >=50% from baseline.

At follow-up, 28 of 30 men had died. The median overall survival was 10.5 months (95%CI: 8.3-12.6).

They concluded thatcompared to the post-chemotherapy phase II study of abiraterone (58 men) their cohort most likely had a larger tumor burden (e.g. higher PSA, more therapies prior to start of ketoconazole). Nonetheless, we found that a reasonably comparable maximum >=50% PSA response-rate (43% in phase II) and three-months response-rate >=50% (36% in phase II). Also a significant decline in ALP was demonstrated with the use of ketoconazole that has not been reported in abiraterone trials.

They concluded that given the large difference in the cost of the two drugs, a head-to-head comparison of abiraterone and ketoconazole in mCRPC men in the post chemotherapy is justified.

This small study did not compare the efficacy of ketoconazole against abiraterone in the pre-chemotherapy space.

This study, as well as a study in the pre-chemotherapy stage of prostate cancer should be peaking the interest of prostate cancer clinicians and government agencies.  If this study can be duplicated in larger trials it could allow a major financial cost savings while not putting at risk any man with prostate cancer.  I wonder why we haven’t heard more about this research.

J Clin Oncol 32, 2014 (suppl 4; abstr 174); M. Andreas Roeder, Kasper Drimer Berg, Daniel Hunde, Camilla Nerstroem, Frederik Birkebæk Thomsen, Klaus Brasso, Peter Iversen; Copenhagen Prostate Cancer Center, Rigshospitalet, Copenhagen, Denmark; Department of Urology, Rigshospitalet, Copenhagen, Denmark; Department of Urology, Rigshospitalet, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Joel T. Nowak, M.A., M.S.W.