Prostate Drug Cuts Cancer Odds, Has Risks
A drug that shrinks the prostate gland can reduce the risk of prostate cancer by about one-fourth, providing the first hope for men who are at high risk of developing the disease. But it is not clear how many men will want to use the drug because of its side effects, according to a major new study.
The drug, called finasteride, would prevent prostate cancer in 15 of every 1,000 men who took it, according to the study, which was halted prematurely because of the drug’s beneficial effects. But some of those who took it had a reduced libido or suffered impotence, a finding that would make the drug less desirable to many potential users.
“These are very important results,” the study’s leader, Dr. Ian Thompson of the University of Texas Health Sciences Center in San Antonio, told a news conference Tuesday. “This is the first intervention that has proved to reduce a man’s risk of prostate cancer.”
The findings could have “extraordinary public health potential” even if the drug is used in only a small fraction of men over 50, he added. An estimated 221,000 American men are diagnosed with prostate cancer each year, making it the most common form of cancer other than skin cancer. About 29,000 die of the disease annually, second only to lung cancer.
But many researchers are not ready to recommend the drug to all their patients.
Some evidence suggests that in addition to the sexual side effects, the drug prevents mainly the less-aggressive, slow-growing prostate tumors that are not a problem for most men. In fact, men who took finasteride were about one-fourth more likely to have aggressive tumors of the type that spread throughout the body and require intervention.
“That doesn’t sound like a very good trade-off to me,” said Dr. Peter Scardino of the Memorial Sloan-Kettering Cancer Center in New York City, who wrote an editorial that will accompany the article when it is published in the New England Journal of Medicine next month.
Doctors don’t yet know, however, whether the drug increases the number of aggressive tumors, selectively prevents only the slower-growing tumors, or simply makes it harder to distinguish between the two.
The researchers said that the men who could benefit the most from the drug are those who are at an especially high risk of developing prostate cancer. That includes African Americans and men who have a brother or father with the disease.
“Millions of men may benefit from finasteride’s ability to reduce prostate cancer risk,” said Dr. Leslie Ford of the National Cancer Institute in Bethesda, Md. But, she added, “the decision to take finasteride is an individual one in which the benefits and risks must be considered.”
Tens of thousands of American men are already taking finasteride in a low-dose form -- 1 milligram -- marketed as Propecia for reducing hair loss. That dose is probably not high enough to have an effect on the prostate, experts said.
Other men are taking a 5-milligram dose of the drug, marketed as Proscar, to shrink enlarged -- but not cancerous -- prostate glands. That is the same dose used in the new study. The drug’s manufacturer, Merck & Co., said Tuesday that it may apply to the Food and Drug Administration for permission to market the drug for use in preventing prostate cancer. But because the drug is already approved for other purposes, physicians are free to prescribe it as a cancer preventive now.
Finasteride blocks an enzyme that the body uses to convert the male hormone testosterone to dihydrotestosterone, a hormone that has been shown to play a major role in the growth of both normal and cancerous prostate tissue. Studies showed that the drug could block the growth of cancerous prostate cells in the laboratory, so researchers decided to test it in humans.
Beginning in October 1993, researchers enrolled 18,882 men over the age of 55, none of whom had prostate cancer. Half were given the 5-milligram dose of finasteride once a day, and half a placebo. They received regular tests to check for the growth of tumors, and each man underwent a biopsy after seven years.
The study was initially designed to continue until May 2004, but was stopped in March when the drug’s effects became apparent.
Over the course of the study, 18% of the men receiving finasteride developed prostate cancer, compared with 24% of those receiving the placebo. The effect was consistent over all age and ethnic groups. Fifteen men in each group died of prostate cancer. Researchers attributed that low number to the fact that all tumors were detected at an early stage.
The incidence of tumors was actually quite high, a fact researchers attributed to the biopsies performed after seven years. Those biopsies revealed, in both groups, many small, slow-growing tumors of the sort that can persist for years or even decades without causing problems.
Cancer doctors are still debating the wisdom of treating such tumors when they are detected. Many, if not most, victims of such slow-growing tumors will die of other causes before the tumors grow large enough to become a problem.
The researchers also found that 37% of the tumors detected in the finasteride group were of the more aggressive form that requires treatment, compared with 22% of those in the placebo group.
According to the National Cancer Institute, in a group of 1,000 men over the age of 63, typically 60 would develop prostate cancer over a seven-year period and 18 would have the aggressive form of the disease. If those same men were given finasteride, 45 would get prostate cancer, and 22 of those would have the aggressive form.
Men taking finasteride had 5% to 13% more sexual problems than those taking placebos, but more than half of both groups exhibited the problems, which are normal complications of aging. The drug did, however, reduce the incidence of urinary problems, another complication of aging.
“I wouldn’t put a patient on finasteride to prevent prostate cancer based on the results of this study,” Scardino said.
Dr. Timothy G. Wilson of City of Hope Medical Center in Los Angeles disagreed. Although Wilson was one of the principal researchers in the study, he said that he had not expected it to be successful and was thus pleasantly surprised at the results. “You really have to take notice of a study like this,” he said. “I will talk to my patients, and discuss the benefits and risks.”
And, he noted, “if they do develop sexual side effects, they will go away if we stop the drug.”