FLUTAMIDE VERSUS ORCHIECTOMY IN THE TREATMENT OF METASTATIC PROSTATE CARCINOMA

Purpose: To compare in a randomized clinical trial the therapeutic eff icacy of the nonsteroidal antiandrogen flutamide 250 mg tid to testicu lar androgen suppression by orchidectomy in patients with metastatic p rostate cancer. Patients and Methods: Between 1989 and 1991, 104 patie nts aged 74 +/- 8 years with newly diagnosed metastatic prostate cance r, an ECOG performance status 0-2 and no prior hormone manipulation or chemotherapy, were randomized to receive flutamide 250 mg tid (54 pat ients) or orchidectomy (50 patients). Patients were evaluated at entry and at months 3, 6, 12, 18 and 24. The primary endpoint was duration of progression-free survival, progression being defined as an increase in PSA >50% over the nadir value at 2 consecutive months or a single PSA rise >50% over the nadir value with another objective parameter. A t progression, the treatment was left to the discretion of the attendi ng urologist. Results: 16 patients (10 flutamide, 6 orchidectomy) are not evaluable. 86 had a minimum follow-up of 36 months, 36/42 and 41/4 4 have progressed in the orchidectomy and flutamide group with a time of failure of 419 and 496 days (p = 0.32); median time to progression was almost identical in both groups (370 vs. 396 days p = 0.9); overal l survival at 69 months irrespective of treatment at relapse was ident ical in both groups. Side effects were dominated by gynecomastia, hot flushes in both groups, breast tenderness and diarrhea in the flutamid e group. Overall, 4 (10%) of the patients in the flutamide group withd rew from therapy because of side effects. The impact of flutamide on s exual potency was not assessed because of the advanced age of the pati ents. Serum testosterone rose by 50% over baseline level at month 3 to plateau at 25% over baseline level at month 12. Conclusion: Although affected by the lack of a clear statistical power due to the small num ber of patients in each arm, this study shows that in spite of a const ant elevation of serum testosterone (25% over baseline) flutamide 250 mg tid may be a reasonable alternative to castraction in highly select ed patients with well to moderatly differentiated low volume metastati c prostate cancer and wishing to avoid the side effects of androgen de privation, provided they are closely monitored and ready to switch to standard androgen deprivation in the presence of untolerable side effe cts or suboptimal treatment efficacy as assessed by the inability to a chieve a low PSA nadir.