By Jon Glass, MD
NYU Medical Center
New York , NY
Phone: 212-263-6267 Fax: 212-263-5715
Last Updated: 2/99
Thalidomide was used widely outside of the United States as a hypnotic/sedative agent in the late 1950s and the early 1960s, but was withdrawn from the market because of the high incidence of severe birth defects attributed to this drug. Thalidomide was never approved in the US until recently, when it was approved for use in the treatment of leprosy-related conditions. However, there has been renewed interest in thalidomide over the past several years, particularly in the treatment of AIDS-related conditions, cancer and HIV-induced wasting, complications of leprosy, and bone-marrow transplant related graft-versus-host disease. These effects were attributed mostly to specific inhibitory activity on tumor necrosis factor-alpha (TNF-alpha) production.
Observations that thalidomide is also an inhibitor of angiogenesis (prevents formation of new blood vessels in tumors) has prompted investigations of its use in the treatment of cancer. In order for a rapidly growing tumor to maintain its growth, a tumor "signals" already existing blood vessels to sprout new branches to feed it. Without a supply of oxygen and other nutrients, tumor growth would be impaired. As a tumor continues to grow, additional blood vessels would need to be formed to sustain new areas of tumor growth.
Clinical trials of thalidomide as a single agent in malignant gliomas that have recurred following radiation therapy have shown evidence of that this drug is active and can produce responses. Thalidomide is currently being tested in combination with a chemotheraputic agent active in malignant gliomas (carboplatin), and single-agent clinical trials are being initiated in the treatment of recurrent brain metastases and in the treatment of recurrent atypical or malignant meningiomas.
Thalidomide is an oral agent. In the ongoing clinical trials for gliomas, meningiomas, and brain metastases, it is taken as a single dose at night. The dose administered is dependent on the trial and is based on body surface area. Toxicities are usually dose-dependent and include drowsiness and constipation (most common) as well as rash and neuropathy (nerve damage) in the arms and legs. The most serious toxicity is the damage that thalidomide can produce in a developing fetus. All women receiving this drug require monthly pregnancy tests (unless not medically necessary). All men and women receiving thalidomide are required to use at least two forms (barrier and hormonal) of contraception.