Utility of dexrazoxane for the reduction of anthracycline-induced cardiotoxicity.
Dexrazoxane is a derivative of the powerful metal-chelating agent ethyl enediamine tetra acetic acid. Its cardioprotective effect is thought to be due to its ability to chelate iron and reduce the number of metal ions complexed with anthracycline and, consequently, decrease the formation of superoxide radicals. Preclinical studies have confirmed that dexrazoxane has significant activity as a cardioprotective agent against anthracycline-induced cardiotoxicity. Dexrazoxane is well-tolerated, with myelosuppression being the dose-limiting toxicity in Phase I trials. The cardioprotective utility of dexrazoxane has been further illustrated in a number of randomized trials. In addition no significant difference in survival has been observed between the dexrazoxane and control arms of these trials but, in one, a significantly lower response rate was observed in the dexrazoxane compared to placebo arm. Further trials are required to evaluate the efficacy of dexrazoxane in hematological malignancies as well as the adjuvant treatment of breast cancer. Its use in the paediatric setting and in the management of elderly patients with cardiac comorbidity also requires investigation. Recently, interest has focused on the use of dexrazoxane as an antidote for anthracycline extravasation. In addition the general cytoprotective activity of this drug requires further assessment, as well as selectivity in this context.
Jones
Robin L
RL
Sarcoma and Drug Development Units, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK. robin.jones@icr.ac.uk
D000368:Aged; D000818:Animals; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002614:Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011929:Razoxane / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D002614:Chelating Agents; D011929:Razoxane