What is thalidomide?

Indications and Procedures

In 1961, a link was established between the use of thalidomide, a mild sedative, and an increase in the frequency of severe defects in newborn babies in Germany, Great Britain, and other countries around the world where the drug had been in use. The “thalidomide babies” had minor defects of the fingers or toes but had major malformations of the limbs, resulting in incomplete or even missing arms and legs. The defects resembled those of a rare genetic disorder known as phocomelia (“seal limb”). Following the tragic discovery that thalidomide is a potent teratogen (a substance that causes a birth defect), use of the drug was discontinued.

In recent years, however, it has been discovered that thalidomide may be a useful therapeutic agent in a number of conditions, including leprosy, several other dermatologic disorders, different types of cancer, and Acquired immunodeficiency syndrome (AIDS). The Food and Drug Administration (FDA) in the United States has approved thalidomide for use in the treatment of leprosy. Studies have demonstrated that thalidomide can inhibit in vitro angiogenesis, the process of formation of new blood vessels. Since many types of cancers require development of new blood vessels for their continued growth, thalidomide may be especially useful in cases where conventional treatments have ceased to be effective. Its use may be indicated in patients either relapsing after high-dose chemotherapy or who are developing serious side effects and are not able to tolerate additional chemotherapy.

Uses and Complications

Since thalidomide is such a powerful angiogenesis inhibitor, it is being used in disorders requiring antiangiogenic therapy. Successful treatments have been made in cases of ovarian cancer, breast cancer, gastrointestinal
carcinoma, renal melanoma, chronic graft-versus-host disease, and multiple myeloma. In some cases, the effectiveness of thalidomide increased when accompanied by other treatments, including immunotherapy, chemotherapy, and surgery.

Thalidomide appears to have few side effects in its new applications, but its return to medical respectability has raised again the specter of “thalidomide babies.” Adverse effects noted in a few patients have included lethargy, constipation, and peripheral neuropathy. The potential problems associated with thalidomide causing a new round of severe birth defects may be a more serious consequence.

Perspective and Prospects

The outbreak of thalidomide-related birth defects in the 1950’s and 1960’s led to the creation of birth defect surveillance programs in many countries. Unfortunately, medical standards and safeguards are not uniformly good, and there already appears to be an increase in birth defects associated with the new applications of thalidomide in South America. It will be necessary to regulate and to monitor closely the prescription, dispensing, and use of the drug. Counseling of patients of childbearing age will be an especially critical component if the tragedy of thalidomide’s history is not to be repeated.

Bibliography

Brynner, Rock, and Trent Stephens. Dark Remedy: The Impact of Thalidomide and Its Revival as a Vital Medicine. Cambridge, Mass.: Perseus, 2001.

Fanelli, M., et al. “Thalidomide: A New Anticancer Drug?” Expert Opinion on Investigational Drugs 12, no. 7 (July 2003): 1211-1225.

Patrias, Karen, Ronald L. Gordner, and Stephen C. Groft. Thalidomide: Potential Benefits and Risks—January, 1963, Through July, 1997. Bethesda, Md.: Department of Health and Human Services, 1998.

Perri, A. J., and S. Hsu. “A Review of Thalidomide’s History and Current Dermatological Applications.” Dermatology Online Journal 9, no. 3 (August, 2003): 5.