title: Dexrazoxane for the prevention of cardiac toxicity and treatment of extravasation injury from the anthracycline antibiotics.
abstract: The cumulative cardiac toxicity of the anthracycline antibiotics and their propensity to produce severe tissue injury following extravasation from a peripheral vein during intravenous administration remain significant problems in clinical oncologic practice. Understanding of the free radical metabolism of these drugs and their interactions with iron proteins led to the development of dexrazoxane, an analogue of EDTA with intrinsic antineoplastic activity as well as strong iron binding properties, as both a prospective cardioprotective therapy for patients receiving anthracyclines and as an effective treatment for anthracycline extravasations. In this review, the molecular mechanisms by which the anthracyclines generate reactive oxygen species and interact with intracellular iron are examined to understand the cardioprotective mechanism of action of dexrazoxane and its ability to protect the subcutaneous tissues from anthracycline-induced tissue necrosis.
authors.affiliation: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. doroshoj@mail.nih.gov
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000378:metabolism; D011929:Razoxane / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D017382:Reactive Oxygen Species; D011929:Razoxane; D007501:Iron