NEW YORK (Reuters Health) – Treatment with dutasteride reduces incident prostate cancers in men with high prostate specific antigen (PSA) levels, according to a report in The New England Journal of Medicine for April 1.
“Many people may have predicted an increase in high-grade tumors as was observed in a prior study with finasteride, because both drugs shrink the prostate and make such cancers easier to find in treated patients,” lead author Dr. Gerald L. Andriole told Reuters Health by email. “Since there was no increase in these tumors, it suggests that dutasteride is actually shrinking them.”
The biggest finding was the “23% reduction in prostate cancer on each biopsy round (there were 2) and no increase in high-grade aggressive tumors,” he said.
The results stem from the randomized REDUCE trial, in which 8122 men received dutasteride (0.5 mg) or placebo daily. Inclusion criteria were age 50 to 75 years, a PSA level of 2.5 to 10.0 ng/mL, and a negative prostate biopsy (6 to 12 cores) within 6 months before enrollment.
Dr. Andriole, from Washington University School of Medicine, St. Louis, and colleagues evaluated the men with 10-core transrectal ultrasound-guided biopsy at 2 and 4 years. Overall, 6729 men had at least one biopsy during follow-up.
During 4 years of follow-up, prostate cancer developed in 659 of 3305 men in the dutasteride group and in 858 of 3424 men in the placebo group, yielding a risk reduction of 22.8% with dutasteride (p < 0.001).
Similar percentages of each group had tumors with Gleason scores of 7 to 10 in years 1 through 4. In years 3 and 4, however, 12 men on dutasteride had tumors with scores of 8 to 10 were compared with 1 in the placebo group.
Among men with cancer, there was no difference between the groups in the mean number of positive biopsy cores, percentage of cores with cancer, or tumor volume. The dutasteride group had lower rates of high-grade intraepithelial neoplasia and atypical small acinar proliferation.
The dutasteride group had a lower rate of acute urinary retention: 1.6% vs. 6.7%, the report indicates.
The side effects of dutasteride were generally consistent with those previously seen in trials of the drug for benign prostatic hyperplasia. The overall rate of cardiovascular events or deaths from cardiovascular events did not differ between the groups, although dutasteride was linked with a higher rate of the composite event of cardiac failure: 0.7% vs. 0.4% (p = 0.03).
The take-home message, Dr. Andriole said, is that “men at increased risk of prostate cancer because their PSA is elevated can reduce their chance of a positive biopsy. This is important as we now know that many of the men who undergo PSA screening and who are found to have cancer may be "overdiagnosed" and "overtreated".
The study was funded by GlaxoSmithKline, which markets dutasteride as Avodart.
N Engl J Med 2010;362:1192-1202.