Combination of low-dose flutamide and finasteride for PSA-only recurrent prostate cancer after primary therapy

To evaluate the efficacy and tolerability of combined finasteride and low-dose flutamide for prostate-specific antigen (PSA)-only recurrence after definitive therapy and to determine the predictors of recurrence-free survival.

Seventy-one men with biochemical recurrence after primary therapy for prostate cancer were prospectively enrolled from 1996 to 1998. Forty-two patients had undergone radical retropubic prostatectomy and 29 had undergone external beam radiotherapy. Radionuclide bone scans and computed tomography of the abdomen and pelvis showed no metastasis. The initial treatment with finasteride (5 mg twice daily) and flutamide (125 mg twice daily) was continued unless participants were unable to tolerate the agents or experienced PSA progression.

At a mean of 44.4 months (range 12 to 92) of follow-up, 54 (76%) of 71 patients were available for measurement of disease status and response to therapy. Three patients had died of unrelated causes; 5 men withdrew from the study because of side effects and 1 patient for protocol violation. Eight patients were lost to follow-up. Twenty-seven patients (38%) continued receiving therapy with no evidence of PSA progression (PSA level less than 0.4 ng/mL), 6 patients maintained a more than 50% reduction in their baseline PSA level at the time of analysis, and 21 (29%) had PSA progression (ie, elevated PSA level on three consecutive tests more than 4 weeks apart). Major side effects were breast tenderness (90%), gynecomastia (72%), gastrointestinal disturbances (22%), fatigue (10%), and decreased libido (4%). The side effects were mild and well tolerated by most patients.

The combination of finasteride and flutamide showed a moderate efficacy in patients with PSA-only recurrence after definitive therapy. The efficacy appears to be greater in patients who can achieve a PSA nadir of 0.1 ng/mL or less after the start of treatment.