Adult urologyEfficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia☆
Section snippets
Material and methods
Dutasteride, 0.5 mg/day, has been found to be safe and effective, reducing circulating DHT levels by 85% at 1 week and by 90% at 2 weeks.12 Consequently, this dose of dutasteride was chosen for three parallel, randomized, placebo-controlled studies of 24 months’ duration (ARIA 3001 [United States only], ARIA 3002 [United States only], ARIA 3003 [19 countries]) covering 400 sites in total that had identical inclusion and exclusion criteria to allow for a preplanned pooling of the data.
The
Patient demographics
A total of 4325 patients were randomized, of which 2951 men (68%) completed the 24-month studies; the reasons for discontinuation are shown in Figure 1. The reasons for discontinuation were only significantly different statistically between the dutasteride and placebo-treated groups for a lack of efficacy (P <0.001). Pooled baseline data for the two treatment arms are displayed in Table I.
Efficacy
Serum DHT changed by a mean of +9.6% versus −90.2% (median of +5.4% versus −93.7%) at 24 months in the
Comment
Previous experience with 5ARIs have demonstrated that they are most effective in the appropriate patient population.19, 21, 22 Hence, the Phase III studies enrolled only men with a TPV of 30 cm3 or greater by TRUS and a serum total PSA level of 1.5 ng/mL or greater (ie, patients likely to have LUTS as a result of BPH and those at increased risk of disease progression).1 To assess the effect of missing data (discontinuations) in these studies, both last observation carried forward analyses and
Conclusions
The results of this study confirm the hypothesis that the almost complete reduction in DHT levels, through inhibition of the 5-alpha-reductase isoenzymes, can prevent the progression of BPH. Thus, dutasteride represents an additional therapeutic option for clinicians and is particularly suited for men with LUTS due to BPH and enlarged prostates (30 cm3 or greater).
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The ARIA/B 3001-3003 trials were sponsored and supported by GlaxoSmithKline, the manufacturer of dutasteride.
- 1
C. G. Roehrborn and G. Andriole are investigators and consultants for GlaxoSmithKline. K. Hoefner and J. C. Nickel are investigators for GlaxoSmithKline. P. Boyle is a consultant for GlaxoSmithKline.