FDA OKs 2-Drug Therapy for Advanced Colon Cancer : Medicine: Studies show that the combination of agents cuts the death rate in patients after surgery. The disease is fatal to 53,000 annually in the U.S.

The Food and Drug Administration Wednesday approved a combination drug therapy to treat advanced colon cancer, a disease second only to lung cancer as the leading cause of cancer deaths in this country.

“I think it’s the most exciting development in colon cancer treatment in many years,” said Dr. Daniel W. Nixon, vice president of professional education for the American Cancer Society. “It has the potential for saving thousands of lives every year.”

The two drugs, levamisole, until now commercially available only to veterinarians to treat intestinal worms, and 5-fluorouracil (5-FU), a well-known anti-cancer drug for more than 30 years, were shown in studies to substantially reduce the death rate after surgery in patients with an advanced stage of the disease known as Dukes’ C. In this stage, the cancer has spread from the colon to nearby lymph nodes.

Without the drugs, patients at this stage--an estimated 21,000 of the 110,000 Americans found each year to have colon cancer--typically have a five-year survival rate of only about 40% after surgery.

Overall, there are more than 53,000 colon cancer deaths annually in the United States.

Dr. Sam Broder, director of the National Cancer Institute, said it is important that information about the drug therapy be widely disseminated to physicians because “there is an important time window” when this combination therapy must begin, which he said is four to six weeks after surgery.

The postoperative drug therapy is “an important advance” because of its impact on decreasing tumor recurrence and mortality in patients in an advanced stage of the disease, said Dr. Michael Friedman, associate director of the cancer therapy evaluation programs of the National Cancer Institute.

Scientists do not understand why the combination of the two drugs is so effective. But in two large clinical trials sponsored by the cancer institute, involving more than 1,700 patients, the drug regimen after surgery reduced deaths by 33% and decreased the recurrence of cancer by 41%.

Those findings were reported last February in the New England Journal of Medicine.

Neither of the drugs has much effect when used alone. Fluorouracil has been used as a palliative treatment for cancers of the colon, breast, stomach and pancreas and has shown some benefit in patients with digestive system cancers.

Studies of the two drugs on Dukes’ B-stage colon cancer, an earlier stage, have been inconclusive. The drug combination does not benefit patients whose colon cancer has spread beyond the lymph nodes, according to the study.

A study is currently under way to determine whether the drug combination can benefit patients with cancer of the rectum, considered a closely related cancer.

Levamisole was developed by screening thousands of compounds for activity against worms in animals and humans.

It was synthesized in 1966 and developed as a treatment for parasites by Janssen Pharmaceuticals of Beerse, Belgium. It has been used for the last 20 years as a treatment for intestinal worms in humans and animals, although until now it was approved in this country only for use in animals. It works by paralyzing intestinal worms so that they are passively eliminated.

“It’s an intriguing combination of two drugs that have not shown much effect by themselves,” said Nixon of the American Cancer Society. “The lesson here is not to give up. The people who tried this combination are to be greatly commended for their ingenuity.”

The FDA said that the cancer institute is currently testing other active chemotherapy combinations for the postoperative treatment of colon cancer.

Broder said that such cancer institute-sponsored trials “represent state of the art treatment--so the next generation of drugs we will be testing will be things we hope will be even more effective.”

The therapy, which lasts one year, involves taking levamisole tablets orally for three consecutive days every other week, with 5-FU taken intravenously once a week. Common side effects include nausea, occasional vomiting, headache, diarrhea, mouth sores and low blood count, the FDA said.

A blood disorder, agranulocytosis, has also been associated with the treatment and caused one death in the cancer institute trials. Because of this, patients taking the treatment must undergo regular blood tests, the FDA said.

Since May, 1989, the FDA has made the drug combination available to more than 4,000 patients with Dukes’ C colon cancer under a program that releases promising but experimental drugs to the desperately ill.

Levamisole is manufactured by Janssen Research Foundation of Piscataway, N. J., and will be sold under the trade name Ergamisol.