Thalidomide: a review of approved and investigational uses.
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-alpha. In addition to its approved indication for ENL, thalidomide has been studied in various other conditions, including graft-versus-host disease, discoid lupus erythematosus, sarcoidosis, relapsed/refractory multiple myeloma, Waldenstrom's macroglobulinemia, myelodysplastic syndromes, acute myeloid leukemia, myelofibrosis with myeloid metaplasia, renal cell carcinoma, malignant gliomas, prostate cancer, Kaposi's sarcoma, colorectal carcinoma, oral aphthous ulcers, Behçet's disease, Crohn's disease, and HIV/AIDS-associated wasting. Adverse events most frequently associated with its use include somnolence, constipation, rash, peripheral neuropathy, and thromboembolism.


CONCLUSIONS
Use of thalidomide is limited by toxicity, limited efficacy data, and restricted access. Evidence of its efficacy in conditions other than ENL awaits the results of controlled clinical trials.
Department of Pharmacy Practice, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts 02115, USA. s.matthews@neu.edu
S James
SJ
Matthews
Christopher
C
McCoy
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003879:Dermatologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007917:Leprostatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D013792:Thalidomide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D003879:Dermatologic Agents; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D007917:Leprostatic Agents; D013792:Thalidomide