Strategies for reduction of anthracycline cardiac toxicity

Anthracyclines are one of the most active classes of antineoplastic compounds. The limiting toxicity of this class of drugs is a cumulative, dose-related diffuse cardiomyopathy, which occurs in up to 20% of patients with a cumulative doxorubicin dose of 450 to 500 mg/m2. Higher incidences of cardiac toxicity have more recently been reported when doxorubicin was combined with other agents such as paclitaxel. Methods to reduce or prevent this toxicity have been a major area of investigation. The use of anthracycline analogs has had limited success. Available data using anthracyclines incorporated into liposomes suggest that cardiac toxicity is significantly reduced. Dexrazoxane, a bisdioxopiperazine that chelates intracellular iron and prevents free radical formation in cardiac muscle, has been demonstrated to be cardioprotective in patients receiving anthracyclines. This article reviews the data regarding the mechanism of anthracycline-induced cardiac toxicity, diagnostic procedures, and methods of reducing this toxicity.