BICALUTAMIDE FOR ADVANCED PROSTATE-CANCER - THE NATURAL VERSUS TREATED HISTORY OF DISEASE

Purpose: To determine the therapeutic effects of bicalutamide 200 mg i n patients with prostate cancers of different hormone sensitivities. M ethods: Patients with progressive prostate cancer were treated with bi calutamide 200 mg daily. Before treatment, patients' tumors were class ified on the basis of prior hormone exposure and by serum testosterone levels into androgen-dependent and androgen-independent groups. Prior exposure to flutamide and response to flutamide withdrawal was also c onsidered. Outcomes were reported independently on the basis of postth erapy changes in prostate-specific antigen (PSA), measurable disease, and radionuclide bone scans. Results: Outcomes varied by prior hormone exposure as a higher proportion of patients with progression of andro gen-dependent tumors showed posttherapy PSA decreases of more than 50% or more than 80%, measurable disease regression, and improvement on r adionuclide bone scans than did patients with androgen-independent pro gression. Within the category of androgen-independent progression, cli nical benefit was observed in patients who had previously progressed o n flutamide, independent of the response to flutamide withdrawal. Pati ents who had progressed on a gonadotropin-releasing hormone (GnRH) ana log alone had a low response proportion, whereas those who progressed after two or more hormone therapies did not respond. Overall, the drug was well tolerated. After progression on bicalutomide monotherapy, on e third of patients with androgen-dependent progression responded to m edical castration with a GnRH analog. Conclusion: Classifying patient tumors on the basis of prior hormone exposure permits a more precise e stimate of the potential benefit of a specific hormone therapy for the individual patient. The precision is further increased by reporting t he effects of a drug on each parameter of disease independently. The d ifference in outcomes for patients with androgen-independent progressi on suggests that the specific hormone therapy administered and the res ponse to that therapy can influence the biology of the relapsing tumor and the sensitivity to subsequent therapies. The sensitivity to bical utamide after progression on flutamide deserves further study. (C) 199 7 by American Society of Clinical Oncology.