Alternative non-steroidal antiandrogen therapy for advanced prostate cancer that has relapsed after initial maximum androgen blockade

Abstract

5135 Background: Large meta-analyses have documented that maximum androgen blockade (MAB) for advanced prostate cancer confers survival benefits. Also, we and others reported the effectiveness of second-line hormonal therapy for prostate cancer that has relapsed after initial hormone therapy. However, there is little clinical evidence on the effectiveness of this latter treatment strategy. Therefore, in the present study, a multicenter trial in Japan, we performed analyses of clinical outcomes following alternation switching from one non-steroidal antiandrogen to another (i.e., bicalutamide (BCL) to flutamide (FLT) and FLT to BCL) for advanced prostate cancer relapsed after initial MAB therapy. Methods: The study included 232 patients with advanced prostate cancer, who had initially been treated with MAB that included surgical or medical castration combined with non-steroidal antiandrogens. First line regimens included either FLT 375 mg/day or bicalutamide BCL 80 mg/day. If a patient relapsed while on 1st line therapy, we discontinued the antiandrogen and evaluated the patient for antiandrogen withdrawal syndrome (AWS). We then administrated an alternative antiandrogen and evaluated its effect. Results: The incidence of AWS after the initial MAB was 15.5% (BCL) and 12.8% (FLT), respectively. The occurrence of a PSA decrease after antiandrogen withdrawal was one of the prognostic factors. Non-steroidal antiandrogens as alternative therapies for patients who relapsed from initial MAB were effective (PSA decrease >50%) in second-line MAB (FLT 34.2%, BCL 43.6%). A total of 142 of 232 patients (61.2%) showed a PSA decrease in response to an alternative antiandrogen and these responders showed significantly better survival than non- responders, suggesting that responsiveness to second-line therapy predicts increased survival. Conclusions: Following up on MAB with an alternative non-steroidal antiandrogen is effective against advanced prostate cancer that has relapsed after initial MAB. Having even a partial response to second-line MAB treatment was associated with improved survival. Our data support the notion that responders to second-line regimens are androgen-independent but still hormonally sensitive. No significant financial relationships to disclose.