A controlled trial of bicalutamide versus castration in patients with advanced prostate cancer

Bicalutamide is a new, potent antiandrogen with potential efficacy in the treatment of men with advanced prostate cancer. Although no pure antiandrogen has been well studied versus castration, potentially fewer adverse effects could occur, making such an agent a potentially useful alternative therapy. To date, three randomized controlled trials have been performed comparing these two treatments. In preliminary studies, a dose of 50 mg bicalutamide per day was selected for these trials. In two of the studies (0302, 0303), this drug was compared to either medical or surgical castration, the latter choice being made by the patient. In the third study (0301), bicalutamide was compared to bilateral orchiectomy.

Using an intention-to-treat format, the outcomes assessed were time-to-treatment failure, time-to-objective disease progression, subjective response, and survival time in men with previously untreated metastatic disease. The incidence of breast tenderness, gynecomastia, and hot flushes was also determined in both treatment arms. A quality-of-life questionnaire was administered on multiple occasions after initiation of therapy.

Based on an analysis of > 1000 patients, the objective and subjective results favored castration over bicalutamide (50 mg/day). The hazard ratios for time-to-treatment failure (1.59), time-to-disease progression (1.62), and median survival (1.44) were all significantly greater in the castration group (P > 0.001). Another difference noted at 3 months was a significantly lower median fall in prostate-specific antigen values in the bicalutamide group (86-88% versus 96-97%). Symptomatic patients receiving bicalutamide were only 0.43 times as likely to have subjective improvement as the patients treated by castration. A comparison of pharmacologic effects showed that only the incidence of hot flushes was lower in the bicalutamide group, whereas breast tenderness and gynecomastia were more common. This difference in hot flushes, however, translated into better quality of life during the first several months with regard to sexual relations and sexual functioning.

Bicalutamide monotherapy at 50 mg/day appears inferior to castration in overall objective and subjective response rates. Whether higher doses of bicalutamide can compete more favorably will need to be tested in further clinical trials.