Thalidomide in multiple myeloma – clinical trials and aspects of drug metabolism and toxicity

Author： Breitkreutz Iris Anderson Kenneth C

ISSN： 1742-5255

Source： Expert Opinion on Drug Metabolism and Toxicology, Vol.4, Iss.7, 2008-07, pp. : 973-985

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Abstract

Background: After the tragic events in the early 1960s, thalidomide has re-emerged as therapeutic for multiple myeloma (MM). It was first approved for the treatment of erythema nodosum leprosum, and is now under evaluation for hematologic and non-hematologic disorders. Its complex mechanism of action is not fully understood; however extensive preclinical studies in MM have revealed its antiangiogenic and immunomodulatory properties. Objective: In this review, we focus on the importance and toxicity of thalidomide in today's clinical use. Methods: Key preclinical and clinical trials available as well as data on the pharmacokinetics and pharmacodynamics of thalidomide in humans are summarized. Conclusions: Thalidomide is widely used as first-line treatment and in relapsed/refractory MM. The most common side effects are fatigue, constipation and peripheral neuropathy, and careful monitoring is required to avoid fetal exposure.