Researchers involved in the international Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial have reported that dutasteride, a 5-alpha-reductase inhibitor that inhibits conversion of testosterone into dihydrotestosterone, was effective in reducing the risk of biopsy-proven prostate cancer in men with an elevated prostate specific antigen (PSA) with negative prostate biopsies. The details of this study were published in the April 1, 2010 issue of the New England Journal of Medicine.1 Preliminary results of this study were reported reported at the Joint ECCO 15 – 34th ESMO Multidisciplinary Congress in Berlin, September 20-24. 

A previous study in average-risk men has shown that finasteride, also a 5-alpha-reductase inhibitor, reduced the incidence of prostate cancer by approximately 25% without increasing the incidence of high-grade cancers. These data were included in four publications published online on May 18, 2008 in Cancer Prevention Research. Finasteride and dutasteride are commonly prescribed for the treatment of benign prostatic hypertrophy (BPH). These drugs may also be useful for the treatment of male pattern baldness, but this is not an approved use by the U.S. Food and Drug Administration (an application is pending, however).

The RECENT trial was a randomized controlled trial sponsored by GlaxoSmithKline, who markets dutasteride as Avodart®. To be eligible for this trial, men between the ages of 50 and 60 years had to have a PSA of 2.5-10.0 ng/mL, and men over 60 years of age had to have a PSA of 3.0-10.0 ng/mL. All subjects had to have negative prostate biopsies within six months. There were 8,121 men enrolled in this study who were randomly allocated to receive four years of treatment with dutasteride or placebo. Eighty-thee percent (6,726) of patients had a follow-up biopsy and were evaluable for efficacy. There were 3,424 patients in the placebo group and 3,305 in the dutasteride group.

• Prostate cancer was diagnosed by biopsy in 659 patients in the dutasteride group compared with 858 in the control group.
• Dutasteride reduced the incidence of biopsy-proven prostate cancer by 22.8% for the entire group.
• Risk reduction was similar for men above and below the age of 60 years.
• Risk reduction was higher in men with a family history of prostate cancer (31.9%).
• Risk reduction was also higher in men with the largest prostate on entry to the study (32.1%).
• The rate of urinary retention in the dutasteride group was 1.6% compared with 6.7% in the control group.
• The risk of urinary tract infections was reduced by 41%.
• The incidence of cardiac failure was 0.7% in the dutasteride group compared with 0.4% in the control group (P=0.03).

Comments: This study shows that dutasteride can reduce or delay the development of prostate cancer in up to one-third of men who have an elevated PSA with negative prostate biopsies. Side effects appear to be minimal, but the risk of cardiac failure was statistically increased.

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