The drug, finasteride -- sold under the brand names Proscar and the better-known Propecia -- has been used for several years to treat enlarged prostate glands and, in lower doses, male baldness. Based on a major new study, finasteride also seems to cut prostate cancer risk by 25 percent.
"That's a profound reduction," said Dr. Peter Scardino, chairman of the department of urology at Memorial Sloan-Kettering Cancer Center in New York City. In the United States alone, a 25-percent cut would mean more than 55,000 fewer prostate cancer diagnoses each year.
Because of the downside, however, the results "definitely (carry) a mixed message," said Dr. Charles Coltman, Jr., director of the San Antonio Cancer Institute and chairman of the Southwest Oncology Group, which conducted the study. "So, we sought the most rigorous peer review we could."
The forum for review that Coltman and colleagues selected for the 7-year, 18,882-man study was the prestigious New England Journal of Medicine. The publication considered the results significant enough to release them Tuesday, more than three weeks early, so clinicians could begin studying the implications. The study will appear in NEJM's July 17 issue.
The study detected prostate cancer in 803 of the 4,368 men in the finasteride group whose data were available for the final analysis. That is about 18.4 percent of the total. Cancer also was found in 1,147 men among the 4,692 men who were taking placebo and could be evaluated -- or 24.4 percent of the group.
"That difference is statistically significant," Coltman said.
However, the men who registered high Gleason scores -– ratings of the potential lethality of their disease –- totaled 6.4 percent of those on finasteride and 5.1 percent of those on placebo. In other words, the risk of more dangerous cancers developing seems to be about 1 percent higher when finasteride is involved.
Because of the increased risk, Coltman and Scardino doubted many doctors will begin prescribing finasteride to battle one of the most puzzling and challenging forms of cancer. Just like so many other issues in contemporary medical treatment -- the controversy that has been simmering the past year over hormone replacement therapy comes immediately to mind -- using the drug involves tradeoffs.
Coltman explained some of those tradeoffs, which men over age 55 will have to discuss with their doctors:
--If 1,000 men take finasteride to reduce an enlarged prostate gland, at the end of seven years, 45 will develop cancer.
--If those same 1,000 men do not take finasteride, 60 will have cancer at the end of the seven years.
--Among the men who develop cancer who took finasteride, 22 will develop high-grade, dangerous cancers.
--Among the men who have cancer but did not take finasteride, 18 will develop high-grade malignancies.
In addition, men who take finasteride will find themselves at increased risk for sexual side effects, although the doctors said those effects, including impotence, also occur normally in men as they age.
"This is a landmark study in many ways," Scardino, professor of medicine at Cornell University in New York City, told United Press International. "I think many of us were surprised that finasteride profoundly reduced cancer in these men."
The biggest problem in dealing with prostate cancer is the wide variety of treatments -– from the most conservative approach of "watchful waiting," which means doing nothing, to radial prostatectomy, the removal of the walnut-sized gland in an operation that can leave a man impotent and incontinent. Yet making more therapy options available generally means creating even more indecision about what course is best.
"Finasteride prevents or delays the appearance of prostate cancer," said Coltman, "but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer."
The report in the New England Journal of Medicine is based on findings involving about half of the participants, or 9,457 men. Because the preliminary results appeared to favor finasteride's anti-cancer benefits over the use of a placebo in other patients, the study, called the Prostate Cancer Prevention Trial -- which was sponsored by the National Cancer Institute in Bethesda, Md. -- was terminated early. The 10-year trial originally was scheduled to end in May 2004.
"The numbers of people taking part in this study are so huge that we think this is a real finding," Scardino said. "We saw this difference across the board. We have to tell patients who are going to take finasteride that there is a one-in-100 chance that they will develop a dangerous cancer -– at the same time we are telling them that taking the drug will result in a 25 percent reduction in getting prostate cancer."
Even though the study involved nearly 19,000 men, it was not large enough or long enough to determine if finasteride improved prostate cancer survival odds. Coltman estimated such a determination would require 15 years of observation and 57,000 participants.
"We will continue to follow these men and see what happens with them," he said. Study patients are being told which group they were in -- finasteride or placebo -- so they can change their medication after consultation with their doctors.
"The study gives us a lot more facts than we had before," Scardino said, "but it doesn't make it any easier to advise our patients what to do. I think I will be able to tell patients who are on finasteride now for control of benign prostate hyperplasia (non-cancerous enlarged prostate) that they do not have to change their medication. However, I think these patients should be monitored closely if they have prostate changes."
Scardino also suggested younger men using Propecia to prevent baldness might be doing themselves a favor by reducing their risk of prostate cancer, but whether that assumption remains valid in the long run will require a larger clinical study.
Both Propecia and Proscar are manufactured by Merck and Company Inc., of Whitehouse Station, N.J.
"If I had patients with a family history of prostate cancer," Coltman said, "I might advise them to take finasteride as a preventive treatment based on these results." However, he noted he and the patient would have to weigh the pros and cons of the study.
Prostate cancer is the most common non-skin cancer, the second leading cause of death from cancer in men and the sixth leading cause of all deaths in the United States.
The number of new cases of prostate cancer, now estimated at more than 220,000 per year, is expected to rise to 380,000 by 2025 because of the aging male population, Scardino wrote in an editorial accompanying Coltman's report. Prostate cancer frequency and mortality rates increase with age. Other major risk factors include family history, ethnicity, and high fat diet. So far, there is no proven means of prevention.
Because prostate cancer is such a common disease, Scardino and Coltman both suggested the new study -- and follow-up data on the study subjects -- will be mined by scientists for nuggets that might help them find new ways to treat the disease in the future.