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August 06, 1999

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NCI's Division of Clinical Sciences Will Test Thalidomide in Patients with Advanced Colon Cancer

The Division of Clinical Sciences at the National Cancer Institute (NCI) is studying the effectiveness of the drug thalidomide in preventing the recurrence of colorectal cancer in patients with advanced disease that has been successfully treated by surgery.

More than 80 percent of colorectal cancer patients will have their disease successfully treated by surgery, but nearly two-thirds of those will have the disease return in the colon or elsewhere. When the disease has spread, tumors can occur in the liver, lung, and other organs. Scientists are searching for treatments to use in addition to surgery to prevent the disease from returning.

The drug thalidomide has been shown to prevent the development of new blood vessels, a process known as angiogenesis. A tumor cannot grow beyond the size of a pinhead without forming new blood vessels to supply its nutritional needs. By blocking the development of new blood vessels, researchers are hoping to cut off the tumor's supply of oxygen and nutrients, indirectly stopping its growth and spread to other parts of the body. In comparison, traditional cancer drugs kill cancer and normal cells directly.

It is the ability of thalidomide to block the development of new blood vessels that likely caused the well-documented limb malformations in babies of mothers who took the drug as a sedative during pregnancy. The drug was used for this purpose for a short time in Europe, but it was never approved for use in the United States. Both men and women taking the drug in cancer treatment trials are required to use two types of contraception to prevent contributing to a pregnancy.

The study is open to men or women who have local recurrence (in the colon) following surgery, or whose colon cancer has spread to liver, lung or other organs, if their current tumors can be surgically removed. After surgery, they will receive either thalidomide or a placebo (an inactive pill that looks like thalidomide) for up to two years to see if the drug prevents the disease from returning. Giving patients either the drug or a placebo, in a manner known as "double blinding" (neither the doctors nor the patients will know whether they are receiving the drug or the placebo), allows the researchers to see the benefits and side effects of thalidomide clearly.

The drug, because it has a sedative effect, is given once daily, at bedtime. The doses of thalidomide will be increased, as long as the patient tolerates it, from 100 mg per day up to 300 mg per day. Thalidomide can also cause peripheral neuropathies - tingling or pain in the hands and feet. The study will include 94 patients and all medical visits will take place at the Bethesda, Md., campus of the National Institutes of Health.

By comparing the effects of thalidomide to the natural course of the disease in those receiving placebo, the scientists will evaluate whether the drug improves disease-free survival in colorectal cancer patients with advanced disease removed by surgery. Additionally, studies will be done to learn more about how thalidomide works in the body.

The researchers will test each patient's blood for proteins (VEGF, bFGF) that are known to activate endothelial cell growth and movement, because endothelial cells are the source of new blood vessels and have a remarkable ability to divide and migrate. They will also look for other markers that may show if a tumor is present or growing (CEA) and for circulating tumor cells in the blood prior to and following surgery.

Patients interested in participating in this trial are urged to call the NCI at 1-888-NCI-1937.

Cancers of the colon and rectum are one of the most frequently diagnosed cancers in the United States (after lung, prostate, and breast cancers), with about 129,400 new cases expected in 1999.

For more information about cancer, visit NCI's Web site for patients, public, and the mass media at http://www.nci.nih.gov.