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Dutasteride for BPH

 

Clinical bottom line

Dutasteride 0.5 mg daily was effective in men with BPH. It improved symptoms and maximum flow rates, reduced prostate volume and episodes of acute retention and prostate surgery. It appears to be as effective as the other 5-alpha-reductase inhibitor, finasteride.

There is preliminary evidence of possible effects on rates of prostate cancer detection.


Reference

CG Roehrborn et al. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002 60: 434-441.

Study

This is a combined analysis of three trials with identical design, two conducted in the USA and one in 19 countries. All trials were randomised, and placebo controlled, and were of 24 months duration. Inclusion criteria were men aged 50 years or older, a clinical diagnosis of BPH, a prostate volume measured by transrectal ultrasound of 30 cc or greater, an AUA score of 12 points or greater (moderate symptoms) and a maximum urinary flow rate of 15 mL/second or less.Exclusions were men with prostate cancer, with a high residual volume, or with previous prostate surgery or acute retention. Also excluded were men with a PSA value greater than 10 ng/mL or lower than 1.5 ng/mL.

There were 4,325 men randomised to dutasteride 0.5 mg daily, or matching placebo. Main endpoints were change in symptom score and risk of AUR. Assessments were made at 1, 3, 6, 12, 18 and 24 months.

Results

The combined study had a quality score of 4/5, a high score minimising bias. The method of randomisation was not given. At baseline men had an average age of 66 years, a symptom score of 17, a maximum urinary flow rate of 10 mL/second, and a mean prostate volume of 55 cc.

Symptoms and flow rate

Over 24 months, the symptom score fell by 4.5 units with dutasteride, significantly more than the 2.3 units seen with placebo. Maximum urinary flow rate increased by 2.2 mL/second with dutasteride, significantly more than the 0.6 mL/second with placebo (Figure 1). These changes were apparent by one month, with differences between dutasteride and placebo of over 1 mL/second by month 12.

Prostate volume did not change with placebo, but fell by 26% in men treated with dutasteride.

Figure 1: Changes in symptom scores and maximum flow rate over 24 months with dutasteride and placebo


Acute retention and surgery

Treatment with dutasteride reduced the risk of acute retention and prostate surgery.

There were 90 episodes of acute retention with placebo (4.2%) and 39 (1,8%) with dutasteride. The relative risk was 0.43 (0.30 to 0.62) and the number needed to treat with dutasteride for two years to prevent one episode of retention was 42 (30 to 74).

There were 89 who underwent prostate surgery with placebo (4.1%) and 47 with placebo (2.2%). The relative risk was 0.53 (0.37 to 0.75) and the number needed to treat with dutasteride to prevent one surgery was 51 (33 to 109).

Adverse events

Dutasteride produced higher rates of sexual adverse events than placebo, at a rate of about twice that with placebo. Absolute rates were low, though, at 7.3% for impotence, 4.2% for decreased libido, 2.3% for gynaecomastia, and 2.2% for ejaculation disorder.

Rates of prostate cancer were 42/2158 (1.9%) for placebo-treated men and 24/2167 (1.1%) for those treated with dutasteride. The numbers are small, but this is a statistically significant reduction (relative risk 0.57; 95% confidence interval 0.35 to 0.94).

All cause discontinuations were 33% with placebo and 30% with dutasteride. adverse event discontinuations were at about 8% in both groups.

Comment

These results are broadly in line with those we have come to expect from finasteride in terms of symptom score, maximum flow rate, prostate volume, and effects on acute retention and prostate surgery. The same can be said for the adverse event rates and discontinuation rates.

The effects on prostate cancer detection are interesting but preliminary. The numbers are small, and the time short. We cannot know at this stage whether the effects of dutasteride on prostate volume merely reduce detection rates rather than cancer rates (though this can be same).

On the basis of this good evidence it would be difficult to conclude that there were major differences between dutasteride 0.5 mg a day and finasteride 5 mg a day for treating men with BPH.