For Peer Review 1 Adrenal androgen levels as predictors of outcome in castration-resistant prostate cancer patients treated with combined androgen blockade using flutamide as second-line hormonal therapy

Objectives We analyzed clinical effects and mechanism of flutamide as a second-line antiandrogen for combined androgen blockade (CAB) in patients with castration-resistant prostate cancer (CRPC) treated with bicalutamide as the first-line antiandrogen. Methods Our study population consisted of 16 patients with CRPC who were treated with flutamide (375 mg daily) as second-line hormonal therapy. Five androgens dehydroepiandrosterone (DHEA), androstenedione, androstenediol, testosterone, and dihydrotestosterone (DHT) were measured for investigating the relationship between plasma androgens and outcome following treatment. Furthermore we measured the adrenal androgen levels in medium of adrenal cancer cell line. Results Second-line hormonal therapy using flutamide resulted in a reduction of the PSA level in 14 (87.5%) of 16 patients. Greater than 50% decline in PSA was observed in 8 (50%) of the 16 patients. Median responsiveness duration was 6.25 months. PSA elevation of baseline androstenediol level was a predictive factor of PSA responsiveness. The lower DHEA group improved duration of responsiveness to flutamide. In vitro, 3 μM Page 4 of 34 International Journal of Urology