Thalidomide: an old drug with new clinical applications.

Thalidomide has several targets and mechanisms of action: a hypnosedative effect, several immunomodulatory properties with an effect on the production of TNF-alpha and the balance between the different lymphocyte subsets and an antiangiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple myeloma, malignant melanoma and systemic signs in cancer) and inflammatory conditions (e.g., Crohn's disease and rheumatoid arthritis). Several side effects are associated with thalidomide. Some are major, such as teratogenicity, peripheral neuropathy and deep vein thrombosis. Somnolence and rash are frequently reported when thalidomide is used at higher doses as an anticarcinogenic agent and can lead to dose reduction or treatment discontinuation depending on severity. Minor side effects include abdominal pain and endocrine disturbances. To prevent the teratogenicity, use of thalidomide is strictly controlled in western countries with close adherence to a birth control programme. Close monitoring for early development of peripheral neuropathy is also recommended.

Development of leukocytoclastic vasculitis in a patient with multiple myeloma during treatment with thalidomide.

Thalidomide, an agent with antiangiogenic and immunomodulatory properties, is therapeutically effective in multiple myeloma, leprosy, and autoimmune diseases. The most common clinical toxicities of thalidomide are constipation, neuropathy, fatigue, sedation, rash, tremor, and edema. We here describe for the first time a patient who developed leukocytoclastic vasculitis during therapy with thalidomide. Of the 260 patients treated with thalidomide in our institution, this is the first patient who developed autoimmune disease. We conclude that patients with malignant disorders who are treated with thalidomide should be carefully monitored for the development of autoimmune disorders. Whether autoimmune phenomena also occur during treatment with new drugs such as PS-341 or potent immunomodulatory agents remains to be evaluated.

Thalidomide: emerging role in cancer medicine.

Thalidomide--removed from widespread clinical use by 1962 because of severe teratogenicity--has antiangiogenic and immunomodulatory effects, including the inhibition of tumor necrosis alpha factor. It has now returned to practice as an effective oral agent in the management of various disease states including erythema nodosum leprosum, for which it was approved by the U.S. Food and Drug Administration in 1998, and more recently certain malignancies, including multiple myeloma. Although thalidomide's mechanism of action remains incompletely understood, considerable insight has been generated by extensive preclinical studies in multiple myeloma. Moreover, clinical trials have confirmed benefit in relapsed disease, and the role of thalidomide in treating newly diagnosed patients is currently under study. Its use in other tumors is under evaluation, with promise in renal cell carcinoma, prostate cancer, glioma, and Kaposi's sarcoma. Activity has also been demonstrated in chronic graft-versus-host disease and in symptom relief as part of palliative care.

The re-emergence of thalidomide: results of a scientific conference.

BACKGROUND: The use of thalidomide during the 1950s resulted in teratogenic effects in thousands of infants. Although thalidomide is currently approved for the treatment of a complication of leprosy, it is commercially available to treat other diseases through a controlled distribution system. This article presents a summary of a scientific conference organized to assess clinical research on thalidomide, its new clinical applications, and the social and ethical implications for its use. METHODS: Summaries of 10 presentations and two panel discussions were developed from the authors's, oral presentations, conference slides, responses to questions, and supporting literature. RESULTS: Thalidomide shows promise in treating several diseases, including HIV/AIDS, rheumatoid arthritis, Crohn's disease, and multiple myeloma. The STEPStrade mark (System for Thalidomide Education and Prescribing Safety) Program has been developed by Celgene, the commercial manufacturer of thalidomide, to ensure compliance with prescription and usage protocols. A surveillance system is also in place to monitor and report compliance patterns. CONCLUSIONS: Despite the tragic past associated with thalidomide, the drug shows promise as a treatment for many clinical disorders. The challenge is to answer lingering questions of risks and benefits through clinical trials and discovery, to monitor participation and compliance with protocols developed to avoid use of the drug during pregnancy, and to continue to search for safer and more effective treatment options.