Research on thalidomide slowed in the 1960s, but never stopped. At least one university in the United States pursues thalidomide research, even though performed by only one tenured professor. The medication is an example of how potentially dangerous compounds can be used therapeutically with appropriate precautions and procedures.
Serious infections including sepsis and tuberculosis cause the level of Tumor necrosis factor-alpha (TNFα) to rise. TNFα is a chemical mediator in the body, and it may enhance the wasting process in cancer patients as well. Thalidomide may reduce the levels of TNFα, and it is possible that the drug's effect on ENL is caused by this mechanism. Thalomid, in conjunction with dexamethasone, is now standard therapy for multiple myeloma.
Thalidomide is also prescribed for its anti-inflammatory effects in actinic prurigo, an autoimmune skin disease.
Thalidomide also inhibits the growth of new blood vessels (angiogenesis), which may be useful in treating macular degeneration and other diseases. This effect helps AIDS patients with Kaposi's sarcoma, although there are better and cheaper drugs to treat the condition. Thalidomide may be able to fight painful, debilitating aphthous lesions in the mouth and esophagus of AIDS patients which prevent them from eating. The FDA formed a Thalidomide Working Group in 1994 to provide consistency between its divisions, with particular emphasis on safety monitoring. The agency also imposed severe restrictions on the distribution of Thalomid through the System for Thalidomide Education and Prescribing Safety (STEPS) program.
Studies carried out in animal models have suggested that the use of combined therapy with thalidomide and glucantime could have a thereapeutic benefit in the treatment of Visceral Leshmaniasis.
Thalidomide and multiple myeloma
Thalidomide was first tested as a single agent for the treatment of multiple myeloma in 1999 for its antiangiogenesis activity. Since then many studies have shown that thalidomide in combination with dexamethasone has increased the survival of multiple myeloma patients. The combination of thalidomide and dexamethasone, often in combination with melphalan, is now one of the most common regimens for patients with newly diagnosed multiple myeloma, with an improved response rate of up to 60-70%. However, thalidomide may also cause side effects such as polyneuropathy, fatigue, skin rash, and venous thromboembolism (VTE), or blood clots, which could lead to stroke or myocardial infarction. Bennett et al. have conducted a systematic review of VTE associated with thalidomide in multiple myeloma patients. They have found that when Thalidomide was administered without prophylaxis, VTE rates reached as high as 26%. Owing to the high rates of VTE associated with thalidomide in combination with dexamethasone or doxorubicin, a black box warning was added in the US in 2006 to the package insert for thalidomide, indicating that patients with multiple myeloma who receive thalidomide-dexamethasone may benefit from concurrent thromboembolism prophylaxis or aspirin. In addition, owing to these side effects, newer drugs, such as a thalidomide derivative lenalidomide (marketed as Revlimid) and bortezomib (marketed as Velcade) have increased in popularity.
Further Reading
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