Thalidomide, a glutamic acid derivative, was withdrawn from clinical use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