Hormones’ role in castration-resistant prostate cancer confirmed

Blockage by the selective inhibitor abiraterone acetate of cytochrome P (CYP) 17 is safe and has significant antitumor activity in castration-resistant prostate cancer, according to a phase I study from the Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom. The data confirm that castration-resistant prostate cancer commonly remains dependent on ligand-activated androgen receptor signaling, study authors say.

Researchers conducted a study involving 21 chemotherapy-naïve men who had prostate cancer resistant to multiple hormonal therapies. The men were grouped into three-patient cohorts that were treated with once-daily, continuous abiraterone through five escalating doses, 250 to 2,000 mg.

Abiraterone administration was associated with increased levels of adrenocorticotropic hormone and steroids upstream of CYP17 and with suppression of serum testosterone, downstream androgenic steroids, and estradiol in all patients. Declines in PSA greater than or equal to 30%, 50%, and 90% were observed in 14 (66%), 12 (57%), and six (29%) patients, respectively, and lasted between 69 and greater than or equal to 578 days. Radiologic regression, normalization of lactate dehydrogenase, and improved symptoms with a reduction in analgesic use were documented.

Antitumor activity was observed at all doses; however, because of a plateau in pharmacodynamic effect, 1,000 mg was selected for cohort expansion to nine patients. Treatment was well tolerated, the researchers said. Their findings are scheduled for publication in the Journal of Clinical Oncology.