Proscar

Monotherapy

Two 1-year, placebo-controlled, randomized, double-blind studies and their 5-year open extensions evaluated Proscar 5 mg/day in patients with symptoms of BPH and enlarged prostates by digital rectal examination.

The double-blind, randomized, placebo-controlled, 4-year, multicenter Proscar Long-Term Efficacy and Safety Study (PLESS) study further evaluated Proscar in 3040 patients 45 to 78 years of age with moderate to severe symptoms of BPH and an enlarged prostate upon digital rectal examination. Patients were randomly assigned 1:1 to receive either finasteride or placebo. Of the 3040 patients, 1883 patients completed the 4-year study.

Effect on Symptom Score 

• Patients in PLESS had moderate to severe symptoms at baseline (mean of approximately 15 points on a 0-34 point scale). 

• Patients randomized to Proscar who remained on therapy for 4 years had a mean (± 1 SD) decrease in symptom score of 3.3 (± 5.8) points compared with 1.3 (± 5.6) points in the placebo group.

• A statistically significant improvement in symptom score was evident at 1 year in patients treated with Proscar vs placebo (–2.3 vs –1.6), and this improvement continued through Year 4.  

• Although an early improvement in urinary symptoms was seen in some patients, a therapeutic trial of at least 6 months was generally necessary to assess whether a beneficial response in symptom relief had been achieved. The improvement in BPH symptoms was seen during the first year and maintained throughout an additional 5 years of open extension studies. 

Effect on Acute Urinary Retention and the Need for Surgery

• In PLESS, efficacy was also assessed by evaluating treatment failures. Treatment failure was prospectively defined as BPH-related urological events or clinical deterioration, lack of improvement and/or the need for alternative therapy. BPH-related urological events were defined as urological surgical intervention and acute urinary retention requiring catheterization. 

• 26.2% of patients treated with finasteride had treatment failure vs 37.1% of patients treated with placebo (relative risk, 0.68; 95% CI, 0.57–0.79; P <.001).

• 4.6% of patients in the finasteride arm had surgical interventions for BPH vs 10.1% in the placebo arm (relative risk, 0.45; 95% CI, 0.32–0.63; P <.001).

• 2.8% of patients in the finasteride arm had acute urinary retention requiring catheterization vs 6.6% in the placebo arm (relative risk, 0.43; 95% CI, 0.28–0.66; P <.001).

Effect on Maximum Urinary Flow Rate

• Maximum urinary flow rate was increased by 1.9 mL/sec in the Proscar arm vs 0.2 mL/sec in the placebo arm. A clear difference was observed between treatment arms by month 4 (1.0 vs 0.3 mL/sec).

Effect on Prostate Volume

• In PLESS, prostate volume was assessed yearly by MRI in a subset of patients. In patients treated with Proscar who remained on therapy, prostate volume was reduced compared with both baseline and placebo throughout the 4-year study. 

• Proscar decreased prostate volume by 17.9% (from 55.9 cc at baseline to 45.8 cc at 4 years) compared with an increase of 14.1% (from 51.3 cc to 58.5 cc) in the placebo group (P <.001). 

• Results seen in earlier studies were comparable to those seen in PLESS. The reduction in prostate volume was seen during the first year and maintained throughout an additional five years of open extension studies. 

Prostate Volume as a Predictor of Therapeutic Response

• A meta-analysis combining 1-year data from seven double-blind, placebo-controlled studies of similar design, including 4491 patients with symptomatic BPH, demonstrated that, in patients treated with Proscar, the magnitude of symptom response and degree of improvement in maximum urinary flow rate were greater in patients with an enlarged prostate at baseline. 

Combination with Alpha-Blocker Therapy

• The double-blind, randomized, placebo-controlled, multicenter Medical Therapy of Prostatic Symptoms (MTOPS) trial evaluated the efficacy of Proscar (average 5 years) in 3047 men with symptomatic BPH for 4 to 6 years. Patients were randomly assigned to receive Proscar 5 mg/day, doxazosin 4 or 8 mg/day, the combination of Proscar 5 mg/day and doxazosin 4 or 8 mg/day, or placebo.

• The primary endpoint was a composite measure of the first occurrence of any of the following five outcomes: a ≥4 point confirmed increase from baseline in symptom score, acute urinary retention, BPHrelated renal insufficiency (creatinine rise), recurrent urinary tract infections or urosepsis, or incontinence. 

• Treatment with Proscar, doxazosin, or combination therapy resulted in a reduction in the risk of experiencing 1 of these 5 outcome events by 34% (P =.002), 39% (P <.001), and 67% (P <.001), respectively.

• Combination therapy resulted in a significant reduction in the risk of the primary endpoint compared to treatment with Proscar alone (49%; P ≤.001) or doxazosin alone (46%; P ≤.001).

• The risk of symptom score progression was reduced by 30% (P =.016), 46% (P <.001), and 64% (P <.001) in patients treated with Proscar, doxazosin, or the combination, respectively, compared to patients treated with placebo.

• Combination therapy significantly reduced the risk of symptom score progression compared to the effect of Proscar alone (P <.001) and compared to doxazosin alone (P =.037).

• In MTOPS, the risk of developing acute urinary retention was reduced by 67% in patients treated with Proscar compared to patients treated with placebo (0.8% for Proscar and 2.4% for placebo). Also, the risk of requiring BPH-related invasive therapy was reduced by 64% in patients treated with Proscar compared to patients treated with placebo (2.0% for Proscar and 5.4% for placebo).