Thalidomide: a review of approved and investigational uses.

Abstract Background: Thalidomide is best known as a major teratogen that caused birth defects in up to 12,000 children in the 1960s. More recently, this agent has been approved by the US Food and Drug Administration for the treatment of erythema nodosum leprosum (ENL) through a restricted-use program. Its immunomodulatory, anti-inflammatory, and antiangiogenic properties are currently under study in a number of clinical conditions. Objective: This article reviews the pharmacology of thalidomide; its approved and off-label uses in dermatologic, oncologic, and gastrointestinal conditions; and adverse events associated with its use. Methods: Relevant articles were identified through searches of MEDLINE (1966–June 2002), International Pharmaceutical Abstracts (1970–June 2002), and EMBASE (1990–June 2002). Search terms included but were not limited to thalidomide, pharmacokinetics, pharmacology, therapeutic use , and teratogenicity , as well as terms for specific disease states and adverse events. Further publications were identified from the reference lists of the reviewed articles. Abstracts of recent symposia were obtained from the American Society of Clinical Oncology Web site. Results: Thalidomide is thought to exert its therapeutic effect through the modulation of cytokines, particularly tumor necrosis factor-α. In addition to its approved indication for ENL, thalidomide has been studied in various other conditions, including graft-versus-host disease, discoid lupus erythematosus, sarever, the ulcers return on drug discontinuation, leading to concerns about long-term use of thalidomide and the risk of peripheral neuropathy. The preliminary results of thalidomide use in patients with Crohn's disease are encouraging; however, further studies are necessary. Case reports and studies in small numbers of patients have shown effectiveness for thalidomide in other clinical conditions. Because thalidomide is highly teratogenic, guidelines for its use must be followed carefully. Thalidomide is a toxic medication, and therapeutic and well-tolerated doses have not been established for any condition except ENL. Because long-term use of thalidomide carries a risk of irreversible peripheral neuropathy and because the neuropathy may be asymptomatic, routine testing is necessary. Efforts to develop agents that retain the efficacy of thalidomide without its unwanted effects are ongoing.