June 24, 2003 - Men who took finasteride, the active ingredient in Propecia - the drug used to treat male pattern hair loss - reduced their chances of getting prostate cancer by nearly 25 percent compared to men who took a placebo, according to results of a national study released today online by the New England Journal of Medicine.

These findings resulted in the early closing of the study, called the Prostate Cancer Prevention Trial (PCPT), which was coordinated by a network of researchers called the Southwest Oncology Group (SWOG) and funded by the National Cancer Institute (NCI). The 10-year trial, involving nearly 19,000 participants nationwide, was originally scheduled to end in May 2004.

"Finasteride is the first drug found to reduce the risk of prostate cancer," said Ian Thompson, M.D., University of Texas Health Sciences Center, who led the study. "The drug worked for men at low risk for prostate cancer, as well as those at high risk." Age, PSA level at enrollment, family history of prostate cancer, and race or ethnicity did not affect the drug's ability to prevent the disease.

"There is a cautionary note," said Thompson. "Men in the study who developed prostate cancer while taking finasteride were more likely to have high-grade cancers, which, when found in the general population, may spread quickly even if the tumors are small. But, more than 97 percent of men who did develop prostate cancer during this study had early-stage cancers, which are most often curable."

The reason men on finasteride had more high-grade tumors is currently unknown, but the researchers are studying several possibilities. The drug affects the appearance of prostate cancer cells, and this may lead to a false estimate of tumor grade, which is determined visually by a pathologist. Another possible explanation being examined is whether finasteride truly causes more aggressive tumors to develop-either by preventing only low-grade tumors, or by making the prostate gland more favorable to aggressive tumors.

Prostate cancer is the most common cancer in men, after skin cancer, and will affect nearly 221,000 men in the United States this year. About 29,000 men will die of the disease. The disease-as well as its treatment, which sometimes leads to impotence, urinary incontinence, and other problems-causes a significant health burden for men.

"These findings highlight the importance of funding clinical trials that focus on prevention," said Elias A. Zerhouni, M.D., director of the National Institutes of Health, of which NCI is a part. "Our ultimate goal is to prevent tumors in the first place."
"This study is one important step toward understanding the complexities of prostate cancer as a disease," said Andrew C. von Eschenbach, M.D., NCI director. "This landmark study and the wealth of information gained from it will provide critical insight for future prevention strategies."

"Millions of men may benefit from finasteride's ability to reduce prostate cancer risk," said Leslie Ford, M.D., associate director for clinical research in NCI's Division of Cancer Prevention, who oversaw PCPT for the institute. "As with any medical procedure or intervention, a decision to take finasteride is an individual one in which the benefits and risks must be considered."

Finasteride, also known as Proscar™, was approved in 1992 at a 5 milligram (mg) dose for treating benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate that can cause problems with urine flow. A few years later, the drug was approved at a 1 mg dose under the brand name Propecia™, to treat male pattern baldness. In PCPT, healthy men ages 55 and older were randomly assigned to take either 5 mg finasteride or placebo daily for seven years. Neither the participants nor their doctors knew which men were assigned to take which pills. This type of study, called a double-blind, placebo-controlled trial, is considered the scientific gold standard for determining if an intervention works.

Men chosen for PCPT showed no evidence of prostate cancer at the start of the trial. To enter the study, men needed to have a normal digital rectal exam (DRE) and a prostate specific antigen (PSA) level of 3 nanograms/milliliter (ng/ml) or less. These tests were repeated annually. The participants also agreed to have a prostate biopsy after they had participated for seven years. At the time the trial ended, about 9,000 men had undergone biopsies.

"We extend our deepest appreciation to the study participants," Thompson said. PCPT researchers will continue to monitor the men who participated in the trial at the more than 200 sites around the country. "What these men have already given us is priceless," said Thompson. "But, we will continue to learn much more. The participants provided us with blood and biopsy samples, and this repository of biological materials will prove invaluable in learning more about the molecular changes that happen as prostate cancer develops."

On March 3, 2003, the Data and Safety Monitoring Committee, an independent body that periodically examined the study, advised that the trial be closed early. The recommendation came because data already collected were sound, and the conclusions were extremely unlikely to change with the addition of more data.

By the close of the study, prostate cancer had been found in about 18 percent of the men who took finasteride, or 803 men out of 4,368. About 24 percent of men who took placebo, or 1,147 men out of 4,692, also had been diagnosed with prostate cancer. Many of the men with cancer had normal DREs and PSA levels, and the disease was found only because the trial required an end-of-study biopsy.

Despite the fact that men taking finasteride had fewer prostate cancers overall, they had a greater proportion of high-grade prostate cancers. Overall, 6.4 percent of men on finasteride (280 men out of 4,368) had high-grade tumors. For men on placebo, 5.1 percent (237 men out of 4,692) had high-grade cancers. Having a low PSA level did not correlate with the development of aggressive tumors-some of the men in both groups of the trial had high-grade disease despite PSA levels that would not have been a concern if the participants had received routine screening outside of the trial.

"Although a larger percentage of men taking finasteride had tumors that appeared to be more aggressive to a pathologist, we do not know if those tumors will act biologically aggressive," said Ford. "We will follow these men long term to determine whether a cancer that looks high grade in a man taking finasteride correlates medically with aggressive disease."

The researchers regularly monitored participants for side effects. Compared to men on placebo, more men taking finasteride experienced sexual side effects at some point during the study. On the other hand, urinary symptoms were reported by more men taking placebo.

"PCPT and its findings mark a milestone for the field of cancer prevention, and we will continue to learn more in the years to come," Ford said. "Finasteride's ability to prevent prostate cancer has the potential to reduce the health care burden for this very common disease. The next time men see their doctors, they may want to talk to them about these findings."

Finasteride is just one agent the NCI has been studying to prevent prostate cancer. Another large prevention study currently underway, the Selenium and Vitamin E Cancer Prevention Trial, or SELECT, is determining if these two dietary supplements can protect against prostate cancer.
SWOG, the same group that coordinated PCPT, is conducting the SELECT study for NCI. "Men can take finasteride and still participate in SELECT," said Charles A. Coltman Jr., M.D., chairman of SWOG and director of the San Antonio Cancer Institute in Texas.

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