USC/Norris Study Finds No Benefit Of Finasteride In Preventing Prostate Cancer In Men At Elevated Risk

LOS ANGELES, Calif., Aug. 1, 1998 -- A new study by USC/Norris Cancer Center scientists raises serious questions about the potential use of the drug finasteride to prevent prostate cancer.

Scientists have theorized that finasteride, sold under the brand name Proscar and commonly used to treat benign prostate disease, might offer men a way to cut their risk of developing prostate cancer.

Yet, "it appears that finasteride may not be effective as a chemopreventive agent against prostate cancer, at least in men with high PSA levels," says Ronald K. Ross, M.D., USC professor of preventive medicine and deputy director of the USC/Norris Cancer Center.

"There may even be a subgroup of patients in whom the drug actually could be harmful," says co-author Richard J. Cote, M.D., USC associate professor of pathology and urology. Ross and Cote, along with Eila C. Skinner, M.D., USC associate professor of urology, led the study, which appears in the first August issue of the British Journal of Cancer.

Prostate cancer is the most frequently diagnosed cancer in the United States, and proves fatal for some 40,000 men each year. At present, there's no proven way to prevent the disease.

USC/Norris researchers have long led research on the role of the male hormones androgens in spurring prostate cancer growth. Ross and his colleagues first proposed that lowering levels of the androgen most active in the prostate, called dihydrotestosterone (DHT), could possibly prevent prostate cancer. Ross' team was also the first to suggest that finasteride, which lowers the levels of DHT by blocking the enzyme that converts testosterone into DHT, might prevent the formation of prostate cancer.

The National Cancer Institute (NCI) is in the midst of a large national clinical trial to determine if finasteride can reduce the incidence of prostate cancer. The seven-year NCI study has enrolled more than 18,000 healthy men with normal PSA levels.

Right now, finasteride, manufactured by Merck & Co., is widely used to shrink the enlarged prostate glands of men with benign prostate hyperplasia and thereby improve symptoms. A lower dose of finasteride was approved by the FDA last year to treat cosmetic, incipient hair loss and is marketed under the brand name Propecia.

Although small, the new USC/Norris study seems especially significant in light of this ongoing trial, researchers say. "Ours are the first data to address the question of whether finasteride prevents disease. The results are not reassuring," Ross says.

In contrast to the NCI study (which is focusing on healthy men), the USC team studied 52 men with elevated blood levels of PSA (prostate specific antigen) whose biopsies showed no signs of prostate cancer. PSA is a protein produced only by prostate cells that doctors use as a broad, though fallible, screen for prostate cancer. Because all of the men in this study had elevated PSA levels, they were considered to have a higher risk of developing prostate cancer than men with normal PSA levels.

Half of the men were treated with finasteride for one year, while the other half received no treatment. At the end of the study, a second biopsy revealed that eight of the 27 men who took the drug had developed tumors, compared to only one of the 25 men in the observation-only group.

To evaluate the drug's ability to block tumor development, Cote, Ross and Skinner tracked key intermediate markers of disease, a novel approach to testing new chemopreventive agents. They measured the participants' blood levels of testosterone, PSA and dihydrotestosterone; they also compared tissue samples from the biopsies at the start of the study to those at the end.

While men in the control group showed no changes in blood levels of PSA, testosterone or dihydrotestosterone, the treated men's PSA levels dropped by 48% and dihydrotestosterone levels fell by 67%. However, men in the treatment group saw their testosterone levels rise by 21% during the study.

The team also looked at tissue samples for a marker of benign disease -- called hyperplastic epithelial tissue -- and two markers associated with increased risk of prostate cancer -- the presence of precancerous lesions known as PIN (prostate intraepithelial neoplasia) and the rate of cell proliferation in the prostate gland. They found that, as expected, finasteride reduced the proportion of the hyperplastic epithelial tissue. But, the drug had no effect on PIN or proliferation, which are more strongly linked to the development of cancer.

The results suggest that though finasteride lowers DHT levels, the net effect of hormones acting on the prostate may be unchanged by the drug, according to Ross. That may be because of rising testosterone levels in the men taking finasteride. Although not as potent as DHT, testosterone can also spur prostate cell growth. "The biology is not as straightforward as many people have assumed," Ross concludes.

Notably, of the eight men who had precancerous lesions at the start of the study and were treated with finasteride, six developed cancer after one year. In comparison, in the no-treatment group, none of the five men with precancerous lesions got cancer. This finding, though in a small sub-group of the men, was statistically significant, leading researchers to write, "finasteride is unlikely to be useful and may even be harmful in men with PIN."

"If finasteride were to have had an anti-cancer effect, it is likely that it would have showed up in these patients," Ross says. The USC team holds off, however, on predicting the results of the national trial. "It is possible that the drug could have a beneficial effect in preventing prostate cancer in some men, though the results of this study suggest that this is unlikely," Ross says.

Richard J. Cote, Eila C. Skinner, Carol E. Salem, Susan J. Mertes, Frank Z. Stanczyk, Brian E. Henderson, Malcolm C. Pike, and Ronald K. Ross. "The effect of finasteride on the prostate gland in men with elevated serum prostate specific antigen (PSA) levels." British Journal of Cancer, 78 (3) August 1998.

To set up an interview with Dr. Ross, Dr. Cote or Dr. Skinner, please call Eva Emerson at 323-442-2830.