Combined low‐dose flutamide plus finasteride vs low‐dose flutamide monotherapy for recurrent prostate cancer: a comparative analysis of two phase II trials with a long‐term follow‐up

OBJECTIVE

To compare the efficacy and tolerability of peripheral androgen blockade using combined low‐dose flutamide plus finasteride vs low‐dose flutamide monotherapy for treating biochemical relapse after the definitive management of prostate adenocarcinoma.

PATIENTS AND METHODS

Fifty‐six men treated for biochemical relapse of prostate cancer were enrolled prospectively in a phase II trial at the Walter Reed Army Medical Center from 1997 to 2001. Thirty‐six men were treated with flutamide (125 mg twice daily) and finasteride (5 mg twice daily), and 20 men received low‐dose flutamide only after biochemical recurrence (prostate‐specific antigen, PSA, level ≥0.4 ng/mL). Cox proportional hazards analyses were used to compare the risk of progression between the groups.

RESULTS

Patients on combined and monotherapy had a median follow‐up of 54 and 43.5 months, respectively. Seven men (19%) in the combined arm remain in the study with no progression, while five (25%) on monotherapy continue and are progression‐free. Men on combined therapy had a greater decrease in their PSA level (P = 0.002). Multivariate analysis showed that men on combined therapy had significantly less risk of progression than men on monotherapy (hazard ratio 0.21, 95% confidence interval 0.07–0.63, P = 0.005). There was no significant difference in the frequency of side‐effects between the groups. Toxicities were reported to be mild.

CONCLUSIONS

Our analysis suggests the therapeutic value of low‐dose flutamide alone or combined with finasteride as first‐line agents in a possible graduated approach for treating PSA‐only recurrent prostate cancer. Due to unwanted metabolic effects associated with traditional hormonal agents, phase III trials comparing both regimens with current therapies are warranted.