Drug duo takes on deadly colon cancer.

Drug duo takes on deadly colon cancer 

A double drug treatment, given soon after surgery to patients with advanced colon cancer, shaves the risk of dying from cancer recurrence by one-third, according to two new reports. The therapy is the first significant advance to help people with late-stage colon cancer fight the specter of a recurrence. Colon cancer can recur when surgeons remove all visible malignancies but can't get microscopic cancer cells that have spread to other parts of the body.

"Although this therapy does not cure all patients, it has significantly improved the outlook for patients whose surgically removed colon cancer was at an advanced stage," says Samuel Broder, director of the National Cancer Institute (NCI), which sponsored both studies. Broder announced the findings this week at a press conference in Bethesda, Md.

In the first study, Charles G. Moertel of the Mayo Clinic in Rochester, Minn., and his colleagues studied 401 people with colon cancer. They randomly assigned patients to a group receiving no further treatment after surgery or to groups receiving additional treatment -- either a veterinary drug known as levamisole or a combination of levamisole and 5-fluorouracil, a federally approved anticancer drug. After five years, the researchers found that the patients on the combination regimen had fewer cancer recurrences than did patients receiving no drugs after surgery. In cases where the cancer did reappear, these patients also experienced longer delays before recurrence. Levamisol alone offered only minor advantages compared with no treatment.

Moertel's team discovered a significant survival advantage for people with Dukes' C colon cancer, in which the malignancy has spread to lymph nodes. They found that 49 percent of such patients who got both drugs survived five years, compared with 37 percent of such patients who got no drug treatment after surgery. They detail their findings in the October JOURNAL OF CLINICAL ONCOLOGY.

Preliminary results from a second study confirm those findings. Moertel, who also directed this study of 1,296 colon cancer patients, says he won't release full details until the results are formally published. He did reveal at the press conference, however, that the postsurgical combination treatment reduced the death rate by at least one-third for Dukes' C patients.

So far, Moertel says, the larger study shows no clear benefit from the double drug treatment for people with Dukes' B colon cancer, in which the cancer has not spread past the colon wall. "We don't know the best way to treat these patients yet," admits Michael A. Friedman of NCI. Further research may show they do benefit from the combination regimen, Moertel says.

NCI officials who reviewed data from both studies recommend that physicians treating patients with Dukes' C colon cancer consider postsurgical treatment with levamisole and 5-fluorouracil. Levamisole, commonly used in the United States to kill worms in animals, is not federally approved for human use. NCI advises physicians to enrol Dukes' C patients in research trials offering the experimental treatment. For those who can't get into a clinical trial, Janssen Pharmaceutica, Inc., a subsidiary of Johnson & Johnson, will provide levamisole to NCI free for distribution through physicians. This week, NCI mailed cancer specialists a clinical alert detailing the treatment advance.

Scientists don't understand how the two drugs work together, but they speculate that levamisole stimulates the immune system and somehow interacts with 5-fluorouracil to destroy cancer cells. Moertel says his team initially tried the double drug experiment in a "desperate search" for an effective chemical weapon against colon cancer. The second leading cause of cancer deaths in the United States, colon cancer kills nearly half those who get it.

Prior to Moertel's studies, small-scale European studies had suggested the drug combination showed activity against colon cancer. But because levamisole has a checkered history -- showing early promise as an anticancer agent but until now failing the test of confirmation -- Moertel expressed surprise at his group's results. NCI officials say the two new studies, taken together, yield strong evidence that the drug combination helps keep Dukes' C colon cancer patients alive longer than any other treatment tested. "We've never had this much data showing this consistent a benefit," Friedman notes.