Chemotherapeutics and cardiac toxicity: Treatment considerations and management strategies

Until recently, most chemotherapy-associated cardiac toxicity that manifested as a reduction in left ventricular ejection fraction was thought to have cardiac effects and long-term sequelae qualitatively similar to those seen with conventional doxorubicin. Thus, it was assumed that most chemotherapy-related cardiac toxicity resulted in cumulative, permanent damage to cardiac myocytes, potentially resulting in congestive heart failure and even death in the more severe cases. However, new insights into the nature of the cardiac toxicity seen with trastuzumab - a monoclonal antibody targeting the human epidermal growth factor 2 (HER2) receptor - indicate that the adverse cardiac effects associated with this drug may be quite different, both quantitatively and qualitatively, than those caused by other drug classes. This paper provides an overview of the distinct mechanisms of chemotherapy-associated cardiotoxicity, along with a description of newer therapies, including dexrazoxane and liposomal anthracyclines, such as pegylated liposomal doxorubicin, aimed at increasing the cardiac safety of these agents in various clinical situations.