Low prostate Ca rate seen in men treated with 5-ARI

A 2-year follow-up of the REDUCE (REduction by DUtasteride of prostate Cancer Events) trial of the 5-alpha-reductase inhibitor dustasteride (Avodart) found that few new prostate cancers were detected during the follow-up period, and no deaths were reported.

The 4-year REDUCE study evaluated prostate cancer risk reduction in men taking dutasteride. REDUCE results showed that dutasteride decreased the risk of biopsy-detectable prostate cancer by 22.8% compared to a placebo group (N Engl J Med 2010; 362:1192-202), but concerns remained about the drug’s effectiveness.

For the follow-up analysis, which is scheduled to be published in the March 2013 issue of the Journal of Urology (Sept. 25, 2012), nearly 2,800 men from the REDUCE study participated, representing extension safety and at-risk populations. In the original study, about half were treated with dutasteride and the remainder received a placebo.

Shortly after the REDUCE study’s conclusion, first author Robert L. Grubb, III, MD, of the Washington University School of Medicine, St. Louis, and co-authors followed participants with a clinic visit. They also conducted up to two annual telephone calls, collecting patient data on prostate cancer events, chronic medication use, PSA levels, and serious adverse events. No drugs were administered and no additional biopsies were performed except those "for cause" when clinically indicated.

Although few new prostate cancers were detected, the former dutasteride group produced double the number of cancers than the former placebo group (14 vs. 7). The authors hypothesized that any prostate cancer that may have been suppressed by dutasteride during REDUCE was no longer being suppressed for those subjects who did not continue on 5-ARI therapy. To some extent, observations during the follow-up study support this concept. Using Gleason scores, no high-grade prostate cancers (Gleason 8-10) were detected. No new safety issues surfaced.

More men from the placebo group underwent biopsy (11.6%) than men from the dutasteride group (7.9%). A higher incidence of prostate cancer (1.3%) was observed in men in the dutasteride group who did not continue 5-ARI treatment. Overall, men in either group who took a 5-ARI during the follow-up study tended to have fewer cancers.

"Although this study provides real-world observational data for subjects who had been randomized to 4 years of dutasteride therapy, it has limitations," said Dr. Grubb. "Men in the at-risk population had a low risk of prostate cancer diagnosis due to several prior negative biopsies and corresponding conclusions are specific to the population studied. In addition, some men who dropped out of REDUCE early may have been off dutasteride treatment for longer than the 2-year observational period."

Dr. Grubb disclosed a financial interest and/or other relationship with GlaxoSmithKline. His co-authors have a financial relationship and/or are employees the company.