CHARACTERIZATION OF PATIENTS WITH ANDROGEN-INDEPENDENT PROSTATIC-CARCINOMA WHOSE SERUM PROSTATE-SPECIFIC ANTIGEN DECREASED FOLLOWING FLUTAMIDE WITHDRAWAL

Purpose: We confirmed the reported rate of prostate specific antigen ( PSA) suppression after flutamide withdrawal in patients with metastati c prostatic carcinoma, increasing serum PSA and tumor progression foll owing treatment with total androgen blockade (castration and flutamide ). The value of clinical variables in predicting the rate of PSA decre ase after flutamide withdrawal was assessed and adrenal androgen metab olism was correlated with the rate of PSA suppression following flutam ide withdrawal. Materials and Methods: A total of 41 consecutive patie nts with metastatic prostatic adenocarcinoma and an increasing serum P SA while effectively castrated (plasma testosterone level less than 50 ng./ml.) who were receiving 250 mg. flutamide 3 times daily was evalu ated prospectively before cessation of the flutamide. Responses were d etermined at 6 weeks. Only 2 of the 41 study patients (3%) had stable disease at 6 weeks, that is they had not met objective criteria for re sponse or progression at analysis. Results: Of 39 patients studied 11 (28.2%, 95% confidence interval 14 to 45%) had a PSA decrease (more th an 50% from baseline) following flutamide withdrawal and they were tre ated with initial complete androgen blockade. Median duration of PSA d ecrease was only 13 weeks (range 7 to 52), and 3 of the 11 patients ha d continued suppression of serum PSA concentrations at 12+, 13+ and 20 + weeks. The serum PSA decrease was associated with improved clinical symptoms, although objective regression of the disease was found in on ly 1 to 2 patients with measurable disease. No statistical correlation between endocrine studies or serum bombesin secretion and PSA decreas e was found, although patients with a PSA decrease after flutamide wit hdrawal tended to have a lower dehydroepiandrosterone concentration th an those with PSA progression. No correlation between known prognostic variables and decreased serum PSA after flutamide withdrawal was dete cted. Conclusions: We confirmed the existence of the reported paradoxi cal PSA decrease in patients with androgen-independent carcinoma of th e prostate, and that the delivery of simultaneous initial flutamide wi th castration predicts for PSA decrease. Individual patients appear to benefit from flutamide withdrawal although the overall impact was sli ght. The differences in frequency compared to those reported by others may be accounted for by patient selection and the number of patients receiving sequential castration therapy followed by flutamide.