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Vitamin A-like drug may ward off cancers.

A synthetic vitamin A-like substance may help stabilize a precancerous condition of the mouth that often afflicts smokers. In fact, researchers believe the new drug treatment may also play a role in preventing full-blown oral cancer and other types of malignancies.

In 1986, a research group at the University of Texas M.D. Anderson Cancer Center in Houston first reported using the synthetic substance, called 13-cis-retinoic acid, to treat leukoplakia - whitish patches of skin in the mouth that can turn malignant.

However, the study also found that in many patients, the precancerous skin patches returned soon after the patients stopped taking the drug. In addition, many study participants reported troubling side effects such as redness of the eyes and dryness of the mouth.

The same team has tackled leukoplakia again. This time, Waun Ki Hong, Scott M. Lippman and their colleagues wanted to see if they could prolong the preventive benefits of the drug while minimizing its side effects.

The team designed a clinical trial in which 53 people with leukoplakia received a very large dose of 13-cis-retinoic acid for three months. Then the researchers randomly assigned the study participants to nine months of maintenance therapy with either a low dose of 13-cis-retinoic acid or beta carotene, a natural vitamin A precursor found in many orange fruits and vegetables.

The Texas group tested beta carotene because it produces virtually no side effects and is converted to vitamin A in the body. Beta carotene and 13-cis-retinoic acid both belong to a family of compounds known as the retinoids. Scientists believe retinoids may help stave off cancer by slowing the growth of premalignant cells.

The new study represents the first long-term comparison of 13-cis-retinoic acid and beta carotene. The researchers found that premalignant changes progressed in just two of 24 patients (8 percent) assigned to 13-cis-retinoic acid. However, the beta carotene strategy didn't pay off: 16 of the 29 persons taking beta carotene (55 percent) experienced a steady advance of their premalignant condition.

Lippman and Hong reported their data last week in San Diego at the joint meeting of the American Society of Clinical Oncology and the American Association for Cancer Research.

About 8 percent of Americans will develop leukoplakia, which often strikes smokers and heavy drinkers. The standard treatment for the condition is surgery, but this approach doesn't work for premalignant patches that have spread over large areas of the mouth.

The new study is part of a body of work that suggest retinoids may help prevent cancer, comments Michael Sporn of the National Cancer Institute in Bethesda, Md. Sporn's own work suggests that retinoids may help spur immature cells to mature and thus stop the out-of-control growth that characterizes cancer.

This preventive strategy may work with other types of cancer as well.

Two years ago, Hong's team reported in the Sept. 20, 1990 NEW ENGLAND JOURNAL OF MEDICINE that 13-cis-retinoic acid helped prevent a second bout with cancer in people who had been treated for head and neck tumors. Such people, who are often smokers, run a high risk of developing another cancer after undergoing surgery to remove their primary tumor, Hong says.

Despite the promise that retinoids display, much work remains before doctors can recommend a cancer-preventing pill for their patients. In the meantime, Sporn warns against popping massive quantities of vitamin A in an attempt to ward off cancer. Large doses of this nutrient can cause liver damage and other severe side effects, he notes.
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Title Annotation:13-cis-retinoic acid, leukoplakia
Author:Fackelmann, Kathy A.
Publication:Science News
Date:May 30, 1992
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