ABIRATERONE SUCCESS CONTINUES

NEW YORK (Reuters Health) Jun 16 - Abiraterone acetate leads to significant declines in prostate-specific antigen (PSA) in men with castration-resistant prostate cancer (CRPC), an aggressive form of that disease. This finding is from a phase I/II, single-center study by U.K. and U.S. researchers published online on May 26 by the Journal of Clinical Oncology.

Abiraterone is a small-molecule inhibitor of the enzyme CYP17, which selectively inhibits the body's synthesis of androgen and estrogen.

Lead researcher Dr. Gert Attard and associates also observed that treatment with abiraterone also decreased circulating tumor cell counts and led to improvements in radiologic assessments of tumors. In addition, they say, the trial confirms that a subgroup of patients with CRPC continue to have hormone-driven disease. And finally, the results show that by adding steroid treatment when abiraterone stops working, it's possible to reverse resistance to the drug and significantly extend clinical response to it.

"Overall," the researchers write, "these data suggest that abiraterone acetate is an effective, well-tolerated treatment,"

"About two-thirds of men experienced significant benefits for an average of eight months," Dr. Attard said in a statement that accompanied the report's publication.

Chief investigator Dr. Johann de Bono of the Institute of Cancer Research, Sutton, Surrey, U.K., told Reuters Health that abiraterone is a "potential game-changer" in the treatment of prostate cancer.

Abiraterone was developed at the Institute of Cancer Research. The study was supported in part by Cougar Biotechnology, Los Angeles.

The phase II (open-label, single-arm) portion of the trial was an expansion of a promising phase I trial reported in 2008. All 42 participants were castrated, and 38 had metastases, primarily in bone and/or lymph nodes. Their median age was 70. All received oral abiraterone 1,000 mg daily in 28-day cycles.

PSA declined at least 50% in 28 of the 42 patients; eight patients had PSA decreases of at least 90%. Of the 24 patients who had measurable disease on CT scan, 9 had tumor regression that constituted a partial response. Further, 16 of these 24 patients showed no evidence of progression at 6 months.

Baseline levels of DHEA, DHEA-S, androstenedione and estradiol were associated with increased likelihood of a PSA decline of at least 50%.

Adding dexamethasone 0.5 mg daily at the time of PSA progression reversed abiraterone resistance in 33% of patients.

The report noted that a multicenter, randomized, double-blind study encompassing more than 1,000 patients is currently evaluating abiraterone plus prednisone versus prednisone versus prednisone plus placebo in CRPC patients who previously received docetaxel.

J Clin Oncol 2009.