2 Drugs Combined Cut Colon Cancer Fatalities

WASHINGTON —  New research shows that a combination of two drugs given after surgery substantially reduces the death rate for patients with advanced colon cancer, the National Cancer Institute announced Monday.

“This is a major advance,” Dr. Samuel Broder, director of the cancer institute, said at a press conference. “The results suggest we might be able to reduce the death rate by as much as one-third.”

Federal health officials said the findings are so compelling that researchers have decided to discontinue comparison portions of the studies in which patients are under observation only with no drug therapy, and will urge those patients to consider taking the combination drug treatment.

Doctors Alerted

Also, Broder said, the cancer institute has alerted 35,000 physicians, surgeons and major institutions treating cancer.

“We are encouraged about this,” said Joanne Schellenbach, a spokeswoman for the American Cancer Society. “There is definitely a need for more armaments in the war against advanced colon cancer.”

In 1989, an estimated 107,000 new cases of colon cancer are expected. Excluding common skin cancers, the combined incidence of colon and rectum cancer--estimated at a total of 151,000 new cases this year--is second only to lung cancer in this country. About 53,500 colon cancer deaths are expected this year.

The studies used levamisole, a drug that has been available in this country only to veterinarians for the treatment of intestinal worms, and 5-fluorouracil (5-FU), a well-known anti-cancer drug for more than 30 years. The drugs were started three to five weeks after surgery and given for one year to colon cancer patients whose cancer had spread to the adjacent lymph nodes, an advanced stage of colon cancer known as Dukes’ C. About 21,000 people will be diagnosed this year with Dukes’ C colon cancer.

In one study, 49% of the patients were alive five years after therapy, contrasted with only 37% of those who received no further treatment after surgery, the scientists said.

In the study, 408 patients with Dukes’ B--an earlier stage--or Dukes’ C colon cancer were randomly chosen to receive either observation only after surgery, levamisole alone or the combination drug therapy. Compared to the post-surgical observation-only group, the patients who received both levamisole and 5-FU had “significantly fewer” tumor recurrences after five years, 55% versus 41%. In cases that did recur, those using the drug combination had longer delays before recurrence--23 months versus 14 months.

Results of the combination therapy on Dukes’ B colon cancer were inconclusive, the researchers said.

Some Patients Not Helped

Also, the treatment is of no benefit to patients whose cancer has spread beyond the lymph nodes, they said.

The study was sponsored by the cancer institute and conducted by the North Central Cancer Treatment Group, under the direction of Dr. Charles G. Moertel, a cancer specialist at the Mayo Clinic in Rochester, Minn. The findings were reported in the current Journal of Clinical Oncology.

“We feel we can come to you with great confidence and tell you we have a treatment of value,” said Moertel, who was at the press conference. “I feel any patient with high-risk colon cancer is really getting short shrift if they are not offered this treatment opportunity,” he said.

A second, larger study that confirms these findings is expected to be published shortly “and provides data to suggest a one-third reduction in the cancer death rate at about 3 1/2 years” after surgery, the researchers said.

This study, also sponsored by the cancer institute, used 1,296 patients between 1984 and 1987, and, like the earlier study, showed that the two drugs taken in combination “reduced recurrence rates, delayed onset of tumor relapse and improved disease-free and overall survival for Dukes’ C patients,” the scientists said.

Researchers said that levamisole used alone showed little benefit and that the combination therapy has not yet shown any value in other stages of colon cancer, or as a treatment for rectum cancer.

5-FU has already shown some benefit in patients with digestive system cancers. Levamisole has been used for the past 20 years as a treatment for intestinal worms in humans and animals, although it is approved in this country only for use in animals.

Last May, at the request of the cancer institute, the Food and Drug Administration approved the expanded use of levamisole for treating colon cancer under a mechanism known as a “treatment IND,” for investigational new drug. The designation allows drug developers to release a potentially promising drug to desperately ill patients before it has been approved, and while research continues.

The drug, made by Paul Janssen Co. of Belgium, will be available to U.S. cancer patients free through the National Cancer Institute until the FDA formally approves it for use in the treatment of colon cancer. 5-FU was developed by Hoffmann-LaRoche Inc. of Nutley, N.J.