ABSTRACT
Thalidomide, a glutamic acid derivative, was withdrawn from clinical use in 1962 due to its severe teratogenic effects. Its recent reinstitution in clinical practice was related to its benefits in leprosy and multiple myeloma. Moreover, the antiangiogenic and immunomodulatory properties of thalidomide have led to its evaluation in several malignant diseases, including myelofibrosis, renal cell cancer, prostate cancer, and Kaposi sarcoma. However, thalidomide use is associated with several side effects: somnolence and constipation are the most common, while deep vein thrombosis and peripheral neuropathy are the most serious. A combination of thalidomide with steroids or chemotherapy is being evaluated in several phase 2 studies. While it is not yet clear whether these combinations will enhance efficacy, they appear to increase the toxicity of thalidomide, and thalidomide analogs are being developed to minimize this toxicity. Ongoing studies will clarify the potential advantages of these agents in the treatment of neoplastic diseases.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Immunosuppressive Agents/adverse effects , Neoplasms/drug therapy , Teratogens/toxicity , Thalidomide/adverse effects , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Clinical Trials, Phase II as Topic , Constipation/chemically induced , Drug Administration Schedule , Drug Eruptions/etiology , Drug Therapy, Combination , Humans , Hypothyroidism/chemically induced , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/therapeutic use , Neutropenia/chemically induced , Patient Selection , Peripheral Nervous System Diseases/chemically induced , Sleep Stages/drug effects , Teratogens/chemistry , Thalidomide/chemistry , Thalidomide/therapeutic use , Time Factors , Venous Thrombosis/chemically inducedABSTRACT
BACKGROUND: Dapsone is used widely in treating ocular cicatricial pemphigoid, leprosy, and dermatologic disorders. Hemolysis is a well-known complication of dapsone therapy. Rarely, neutropenia or agranulocytosis may occur, resulting in up to a 50% mortality rate. To the authors' knowledge, agranulocytosis has not been reported in patients treated with dapsone for ocular cicatricial pemphigoid. METHODS: The authors report two cases of dapsone-induced neutropenia with bone marrow suppression in patients with ocular cicatricial pemphigoid. RESULTS: Neutropenia was detected on routine laboratory examination 8 and 10 weeks after initiating dapsone therapy. Bone marrow biopsy showed acellular or hypocellular marrow. Leukocyte count returned to baseline value after cessation of dapsone. CONCLUSION: Patients with ocular cicatricial pemphigoid who were treated with dapsone are at increased risk for agranulocytosis. Dapsone-induced neutropenia may not be a dose-dependent phenomenon. The authors indicate that there is a need for routine monitoring of leukocyte counts, especially 8 to 10 weeks after initiating therapy. Signs or symptoms of infection require immediate investigation.