Dexrazoxane

Abstract

Dexrazoxane (Cardioxane, Zinecard, a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced cardiac toxicity. Dexrazoxane is approved in the US and some European countries for cardioprotection in women with advanced and/or metastatic breast cancer receiving doxorubicin; in other countries dexrazoxane is approved for use in a wider range of patients with advanced cancer receiving anthracyclines. As shown in clinical trials, intravenous dexrazoxane significantly reduces the incidence of anthracycline-induced congestive heart failure (CHF) and adverse cardiac events in women with advanced breast cancer or adults with soft tissue sarcomas or small-cell lung cancer, regardless of whether the drug is given before the first dose of anthracycline or the administration is delayed until cumulative doxorubicin dose is > or =300 mg/m2. The drug also appears to offer cardioprotection irrespective of pre-existing cardiac risk factors. Importantly, the antitumour efficacy of anthracyclines is unlikely to be altered by dexrazoxane use, although the drug has not been shown to improve progression-free and overall patient survival. At present, the cardioprotective efficacy of dexrazoxane in patients with childhood malignancies is supported by limited data. The drug is generally well tolerated and has a tolerability profile similar to that of placebo in cancer patients undergoing anthracycline-based chemotherapy, with the exception of a higher incidence of severe leukopenia (78% vs 68%; p < 0.01). Dexrazoxane is the only cardioprotective agent with proven efficacy in cancer patients receiving anthracycline chemotherapy and is a valuable option for the prevention of cardiotoxicity in this patient population.