We prospectively studied the usefulness of chlormadinone acetate (CMA) as an alternative therapy for prostate cancer relapse after combined androgen blockade (CAB) therapy. Sixteen patients with relapsed prostate cancer after treatment with CAB, including surgical or medical castration and nonsteroidal antiandrogens, 80 mg bicalutamide daily or 375 mg flutamide daily, were enrolled. After discontinuing the antiandrogen for evaluating the patient for the antiandrogen withdrawal syndrome, we administered 100 mg CMA daily as alternative antiandrogen and estimated its effect. Four patients showed a > or = 50% decline in prostate-specific antigen (PSA) levels and another 4 patients showed a < 50% decline in PSA levels but residual 8 patients showed no decline in PSA levels. In 8 patients with a decline in PSA levels, the median duration of alternative CMA therapy was 11.4 months. Patients with a PSA level of < 1 ng/ml at the start of CMA therapy showed the tendency of decline in PSA levels. In contrast, patients with a nadir PSA level of > or = 0.2 ng/ml during pretreatment showed no effectiveness of the alternative CMA therapy. The alternative CMA therapy may be useful in a part of patients with prostate cancer relapse after CAB therapy.