Thalidomide in multiple myeloma--clinical trials and aspects of drug metabolism and toxicity.
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.
Breitkreutz
Iris
I
Dana-Farber Cancer Institute, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. Iris_Breitkreutz@dfci.harvard.edu
Anderson
Kenneth C
KC
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy*; D011247:Pregnancy; D013792:Thalidomide / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D007166:Immunosuppressive Agents; D013792:Thalidomide