A four-year study of more than 8,000 men between the ages of 50 to 75 who had an elevated risk for developing prostate cancer found that those who took the drug dutasteride (sold as Avodart) were less likely to develop prostate cancer than those taking a placebo. What’s more, study participants taking dutasteride were significantly less likely to develop tumors of mid-range severity—or the type that grow unpredictably and may or may not become more dangerous. The study was conducted by an international team of researchers led by Dr. Gerald L. Andriole from Washington University School of Medicine in St. Louis and published in the New England Journal of Medicine. Its findings suggest that dutasteride—which was approved by the U.S. Food and Drug Administration in 2001 for treatment of non-cancerous swollen prostate—may reduce the risk for prostate cancer in some men by shrinking tumors or inhibiting their growth.
Previous research found that a similar drug, finasteride—which is also prescribed to treat benign enlarged prostate—reduced patients’ risk for developing prostate cancer, but this latest study suggests that dutasteride may reduce risk somewhat more. The clinical trial, funded by Avodart manufacturer GlaxoSmithKline, included participants from 42 countries. All men included in the trial showed a heightened risk for prostate cancer—based on elevated levels of prostate-specific antigen (PSA)—but did not yet have any signs of tumors in biopsies conducted in the six months leading up to the trial. Two years into the trial, and again at its conclusion, study participants had biopsies to test for tumors. Researchers found that 858 men (25.1%) in the placebo group went on to develop prostate cancer, compared with 659 men (19.9%) in the group taking dutasteride.
Researchers found that dutasteride seemed to be most effective at limiting the development of tumors of mid-range severity, whose growth can be unpredictable. (This lack of predictability often prompts men to seek treatment, exposing them to potential side effects including incontinence and impotence.) The aggressiveness of tumors is classified between 1 to 10 on what is known as the Gleason scale, where 10 is the most aggressive. The trial showed that men taking dutasteride had the most significant reduction in risk for tumors classified as 5-6 on the Gleason scale. Similarly to data seen in medical practices, researchers found that 70% of all study participants who developed prostate cancer had mid-range tumors (5-6 on the Gleason scale). But, significantly, the prevalence of those tumors differed between the placebo and dutasteride groups. While 18.1% of men in the placebo group developed mid-range tumors, just 13.2% taking the drug did.
While the researchers noted no statistical difference in the development of highly aggressive tumors (Gleason score 7-10) between the placebo and dutasteride groups, after three and four years, they did find a higher incidence of the most aggressive tumors (Gleason score 8-10) among study participants taking the drug—with 12 such tumors in the dutasteride group, compared with just one in the placebo group. The researchers attribute this in part to the fact that men who may have been diagnosed earlier with a mid-range tumor may have continued in the trial, and developed more severe tumors by the time of later biopsy (something seen in previous research as well, and referred to as “tumor upgrade.”) Additionally, because dutasteride shrinks the prostate, biopsies performed on men taking the drug tend to be more accurate than those performed on men with enlarged prostates, study author Andriole says. In supplementary research, the study authors analyzed data, controlling for prostate size at the time of biopsy. These results found that men taking dutasteride had fewer aggressive tumors. Yet, despite those findings, researchers concede that this study doesn’t rule out the possibility that “the difference in the number of cancers with a Gleason score of 8 to 10 was due in part to dutasteride therapy.”
Researchers also found a slightly elevated risk for heart failure in men taking dutasteride—while .7% of men taking the drug had heart failure during the study period, .4% taking placebo did. (In additional research, the study authors found that this elevated risk was most noticeable in men taking dutasteride as well as alpha blockers, which can be prescribed to treat conditions such as high blood pressure and swollen prostate.)
The researchers did confirm that dutasteride was effective at reducing swollen prostate and associated symptoms, such as difficulty urinating and urinary tract infection. While additional research may be necessary to determine how dutasteride may influence risk for the most aggressive form of prostate tumors, researchers concluded that the significant overall reduction in prostate cancer risk among men taking the drug suggested that it “may be considered as a treatment option for men who are at increased risk for prostate cancer.”