A drug widely used to shrink enlarged prostates has been shown to lower the risk of prostate cancer by 23 percent in men who have an increased risk of the disease, according to results of an international clinical trial presented April 27 at the American Urological Association’s annual meeting in Chicago.
The four-year, phase III trial, known as REDUCE (Reduction by Dutasteride of Prostate Cancer Events), is the first to look at chemoprevention for prostate cancer in men at increased risk for the disease. The trial involved 8,200 men ages 50-75 who were randomly assigned to receive a placebo or a daily 0.5 mg dose of dutasteride (Avodart), manufactured by GlaxoSmithKline.
“Dutasteride has the potential to offer many thousands of men a way to reduce their risk of being diagnosed with prostate cancer,” said lead investigator Gerald Andriole, M.D., chief of urologic surgery. “This should ultimately mean more men will avoid treatment for prostate cancer and the cost and unwanted side effects associated with treatment.”
Men in the study had elevated PSA levels (2.5-10 ng/ml), indicating they were at increased risk of prostate cancer. They also had undergone biopsies that found no evidence of cancer within six months prior to enrolling in the trial. Therefore, these men either did not have prostate cancer or possibly had microscopic tumors that were too small to be detected by the pre-study biopsy.
The investigators performed scheduled biopsies on the men two years after they enrolled in the study and again after four years. After two years, prostate cancer was found in 17.2 percent of the men who took a placebo, compared with 13.4 percent who took dutasteride. After four years, prostate cancer was diagnosed in another 11.8 percent of men who received a placebo and 9.1 percent who received dutasteride.
“In these men, the most likely explanation is that dutasteride worked by shrinking tumors and/or slowing their growth, thereby making them less likely to be detected by a biopsy,” Andriole said.
The reduction in prostate cancer risk was constant across multiple subgroups of men in REDUCE — dutasteride worked well in men regardless of age, prostate size, PSA level and family history of prostate cancer.
The U.S. Food and Drug Administration approved dutasteride in 2001 for the treatment of benign prostatic hyperplasia (BPH). This condition causes frequent urination that is difficult or painful. The study was conducted because data collected as part of the FDA-approval process suggested that men with BPH who took dutasteride had fewer diagnoses of prostate cancer.
The investigators found no significant increase in aggressive tumors among men who took dutasteride. This outcome was closely watched because an earlier trial of a similar BPH drug — finasteride (Proscar) — for the prevention of prostate cancer found that while the drug lowered cancer risk, it was linked to more aggressive tumors, although a later analysis of the data suggested that may not be the case.
Over the course of the study, 6.8 percent of men in the placebo group and 6.7 percent of men in the dutasteride group were found to have aggressive, high-grade tumors.
“We are very encouraged by this finding,” Andriole said. “Clearly, the data show dutasteride did not lead to more high-grade tumors, even though they would have been easier to detect in the dutasteride-treated men due to their smaller prostates.”
Prostate cancer and BPH both can raise PSA levels. Dutasteride blocks two forms of the enzyme 5-alpha reductase, which converts testosterone produced in the testicles into dihydrotestosterone. In contrast, finasteride only inhibits one form of the enzyme. Dihydrotestosterone is known to be a potent stimulator of benign prostate growth and the development of prostate cancer.
The REDUCE investigators also found that dutasteride significantly reduced episodes of urinary retention and the need for surgery to alleviate BPH in men taking the drug compared with those taking a placebo.
Prostate cancer is the second most deadly cancer in men after lung cancer. Worldwide, it is responsible for more than 221,000 deaths annually.
The REDUCE trial was conducted at 250 sites in 42 countries. GlaxoSmithKline funded the study. Andriole is chairman of the REDUCE steering committee and a consultant for the company.