University of Virginia Health System

First Prostate Cancer Prevention Drug Found

Study Also Shows A Down Side

< July 9, 2003 >A drug used to combat male baldness and to shrink benign prostate glands also prevents prostate cancer, according to the results of a new study sponsored by the National Cancer Institute (NCI).

Men who took the drug finasteride for seven years had a 25 percent smaller chance of developing the disease during the trial, which was halted 15 months early because of the promising results.

"This trial proves that prostate cancer, at least in part, is preventable," said Dr. Peter Greenwald, director of the Division of Cancer Prevention and Control at the NCI. Dr. Greenwald was also a participant in the trial.

"It is a huge step forward for cancer research," Dr. Greenwald says.

According to the American Cancer Society (ACS), prostate cancer is the second most common cancer in men, affecting more than 220,000 men in the US each year. Of those, roughly 29,000 will die of the disease. Many of the rest may suffer a variety of nonlethal but troubling symptoms, ranging from sexual dysfunction to urinary incontinence.

New Findings Come With Cautions

Finasteride is the first drug shown to prevent prostate cancer, but a few potentially significant hitches exist, the researchers noted at a news conference.

Although the men who took the medication had fewer prostate tumors, those tumors that did develop seemed slightly more likely to be especially aggressive. And, the drug was linked to an increase in such sexual side effects as impotence, a reaction that might deter some men from taking it.

Finally, the researchers said, there is no evidence yet that taking finasteride over time can reduce the death rate from prostate cancer.

That question "is impossible to answer at this time," said Dr. Leslie Ford, a researcher at the NCI, and a co-author of the study.

A report on the findings will appear in the New England Journal of Medicine, but the journal posted the paper on its Web site early because of the clinical significance of the results.

Finasteride (Proscar® and Propecia®) is made by Merck & Co., which provided the drug used in the study. It has been approved by the Food and Drug Administration (FDA) for use in male pattern baldness and benign prostatic hyperplasia (BPH).

Finasteride does not have FDA approval for use in prostate cancer prevention, but Merck plans to present this drug for approval.

The results of the study suggest that finasteride could prevent or delay 15 cases of prostate cancer in every 1,000 men who take the drug, Dr. Ford says. However, it might lead to an additional four cases of aggressive tumors in the men who develop the disease.

The ACS issued a cautious statement about the findings.

"The study will no doubt prompt a lot of men to start asking their doctors whether they should be on the drug, and we would encourage men to carefully weigh their options as this information is very new," said Dr. Harmon Eyre, ACS's chief medical officer.

"There are still some important unanswered questions, especially regarding side effects, whether it can benefit men at increased risk, especially African Americans, who are twice as likely as white men to die of prostate cancer, and the mechanism by which men taking the drug develop higher-grade tumors."

Study Authors Impressed With Results

But Dr. M. Scott Lucia, another co-author of the study and a pathologist at the University of Colorado in Denver, says the link between finasteride and so-called "high-grade" tumors is not well understood. Although the drug could be spurring the growth of these cancers, Dr. Lucia and his colleagues do not think that is happening.

Instead, Dr. Lucia said, finasteride may be altering the appearance of prostate cancer cells under a microscope so that they resemble aggressive tumors but do not act like them.

Finasteride blocks an enzyme that converts the male sex hormone testosterone into dihydrotestosterone, or DHT, a potent form of the molecule that is common in the prostate.

Many prostate tumors are sensitive to DHT. Indeed, men with a genetic defect that keeps them from making the hormone do not get the disease, and a frequent treatment for the tumors is "chemical castration" to deprive the body of sex hormones.

The government study, known as the Prostate Cancer Prevention Trial, started with almost 18,900 men aged 55 and up with no signs or symptoms of prostate cancer. Half were given 5 milligrams a day of finasteride, and half took placebo, or inactive pills.

At the end of the study, about 9,000 men remained; many of the others had dropped out, been excluded from finishing by the early end, refused a final tissue sample, or died.

Among the men who did not get finasteride, 24 percent developed prostate cancer, compared with 18 percent of those taking the drug - a 25 percent difference. Of those tumors, 6.4 percent in the men on finasteride were considered aggressive when a biopsy was done, and about 5 percent in the group that was not taking the drug were considered aggressive.

Dr. Ian M. Thompson, a urologist at the University of Texas Health Science Center in San Antonio, and leader of the research, said men and their physicians will need to assess the risks and benefits of taking finasteride to prevent prostate cancer.

Men with a strong family history of the disease and African-American men in particular, whose risk of dying from prostate cancer is nearly twice that of Caucasians, may be inclined to embark on the therapy, Dr. Thompson said. Similarly, men who are concerned about their risk of the disease for other reasons also may want to consider the drug, he said.

Always consult your physician for more information.

Online Resources

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American Cancer Society

Centers for Disease Control and Prevention (CDC)

Men's Health Network

National Cancer Institute (NCI)

National Institutes of Health (NIH)

New England Journal of Medicine

US Department of Health and Human Services (HHS)

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What Are Risk Factors for Prostate Cancer?

In general, all men are at risk for prostate cancer. However, there are specific risk factors that increase the likelihood that certain men will develop the disease, including the following:

age
Age is a risk factor for prostate cancer, especially men age 50 and older. More than 80 percent of all prostate cancers are diagnosed in men over the age of 65.

race
Prostate cancer is nearly twice as common among African-American men than it is among Caucasian-American men. Japanese and Chinese men native to their country have the lowest rates of prostate cancer. Interestingly, when Chinese and Japanese men immigrate to the US, they have an increased risk and mortality rate from prostate cancer, when compared to their native populations.

diet
Studies suggest that the diet consumed in Western industrialized countries may be one of the most important contributory factors for developing prostate cancer. Consider the following information regarding diet and its effect on the risk for prostate cancer:

• fat
  Studies suggest that men who eat a high-fat diet may have a greater chance of developing prostate cancer.
  
  
• fiber
  Dietary fiber intake may influence circulating levels of testosterone and estradiol, which, in turn, may decrease the progression of prostate cancer.
  
  
• soy protein
  Besides lower fat intake, another major difference between Asian and American diets is the consumption of soy, averaging 35 g/day per capita. Soy contains isoflavone which, in several studies, have been found to inhibit the growth of prostate cancer.
  
  
• vitamin E and selenium
  Vitamin E, an antioxidant, combined with selenium, has been shown to inhibit tumor growth in laboratory animals.
  
  
• carotenoids
  Carotenoids containing lycopenes have been shown to inhibit the growth of human prostate cancer cells in tissue cultures (cells grown in the laboratory). The primary source of lycopenes is processed tomatoes in tomato juice and tomato paste.
  
  
• herbal preparations
  Combination herbal preparations should be used with caution as reported side effects have included venous thrombosis, breast tenderness, and loss of libido. Many herbal preparations have not been studied in men with prostate cancer.
  

obesity
Obesity not only contributes to diabetes and high cholesterol, but has also been associated with some common cancers, including hormone-dependent tumors such as prostate, breast, and ovarian cancer.

environmental exposures
Some studies show an increased chance for prostate cancer in men who are farmers, or those exposed to the metal cadmium while making batteries, welding, or electroplating. Additional research is needed in this area to confirm whether this is a true association.

having a vasectomy, BPH (benign prostatic hyperplasia), or STD (sexually transmitted disease)
Researchers have looked at whether men who have had a vasectomy, BPH, or those who have been exposed to a sexually transmitted disease are at increased risk for prostate cancer. Some studies suggest a link, while others do not support these claims.

family history of prostate cancer
Having a father or brother with prostate cancer doubles a man's risk of developing this disease. The risk is even higher for men with several affected relatives, particularly if the relatives were young at the time of diagnosis.

Geneticists (physicians and scientists who study inheritance and the causes of genetic disease) divide families into three groups, depending upon the number of men with prostate cancer and their ages of onset, including the following:

• sporadic - a family with prostate cancer present in one man, at a typical age of onset; sporadic means occurs by chance.
  
  
• familial - a family with prostate cancer present in more than one person, but with no definitive pattern of inheritance and usually an older age of onset.
  
  
• hereditary - a family with a cluster of three or more affected relatives within any nuclear family (parents and their children), a family with prostate cancer in each of three generations on either the mother or father's side, or a cluster of two relatives affected at a young age (55 or less). Five to 10 percent of prostate cancer cases are considered hereditary.
  

genetic factors
Some genes, when altered or mutated, give a higher risk for uncontrolled cell growth, which, in turn, can lead to tumor development. These genes have various names, but overall are referred to as "cancer susceptibility genes." Approximately 9 percent of all prostate cancers and 45 percent of cases in men younger than age 55 can be attributed to a cancer susceptibility gene that is inherited as a dominant trait (from parent to child).

Always consult your physician for more information.