Background: Abiraterone inhibits the conversion of steroids to androgens by blocking 17a hydroxylase. It was initially shown to be effective in 62% of androgen-resistant prostate cancer (ARPC) with a median duration of 11 months in patients who failed docetaxel. We felt that abiraterone might be more effective in treating asymptomatic ARPC.
Methods: Since June 2011, 45 veterans with ARPC were treated with abiraterone and prednisone bid. The criteria for treatment were a prostate-specific antigen (PSA) level of > 10 or a PSA doubling time of < 6 months. All patients were castrated (testosterone < 50 ng/dL). Response was determined by PSA increase. In patients with significant hyperglycemia, prednisone was reduced to 2.5 mg bid. Thirty-one asymptomatic patients were segregated into 3 groups: increasing PSA only (11), bone-only disease (15), and nodal disease (5). Fourteen symptomatic patients were segregated into 3 groups: bone only (3), nodal disease (6), and visceral metastasis (5). Patients failing abiraterone were treated with enzalutimide. The response was retrospectively analyzed through June 1, 2015.
Results: Forty-three patients were evaluated. The overall PSA response rate (RR) to abiraterone was 55% with a median duration of 9 months. The RR in asymptomatic patients was 61% vs 43% in symptomatic patients. The median duration of response for responders was 16 months (9-48+ months); asymptomatic (19) vs symptomatic (12). Fifteen of 25 responders remained on abiraterone. Eleven of 13 nonresponders died; 8 of 30 responders died. Nine nonresponders had reduced PSA doubling times. The prednisone dose did not affect response but did affect hyperglycemia. No patients subsequently treated with enzalutimide responded.
Conclusions: The RR and duration in asymptomatic patients far exceeded that of symptomatic patients. Reducing prednisone to 2.5 mg bid reduced toxicity. Abiraterone may achieve palliation without a significant biochemical response. Sequential treatment with abiraterone then enzalutimide does not seem to be effective.
