Cardioprotection Using Doxorubicin: The Role of Dexrazoxane

Abstract

Doxorubicin is among the most effective chemotherapeutic agents, and is active against a wide variety of cancers. However, it also is highly cardiotoxic so that any effective use of this agent requires a strategy to limit the toxicity. Dexrazoxane is the only drug approved specifically to counter the cardiac toxicity of doxorubicin because of its ability to interfere with the molecular mechanisms causing the cardiac injury. Although other mechanisms, namely iron chelating properties, were originally thought to be responsible for its cardiac protection, recent studies suggest that dexrazoxane’s interaction with topoisomerase II, an enzyme important for the function of DNA during mitosis is most likely the major mechanism. While it had been thought that the mechanism of doxorubicin’s cardiac toxicity and the mechanism of doxorubicin’s tumor effectiveness are different, more recent studies have suggested that some of the most important mechanisms are similar. Because of this uncertainty, dexrazoxane is underutilized in patients where it could be useful. Thus, studies comparing tumor efficacy in patients taking doxorubicin randomized to dexrazoxane comparing progression-free survival and mortality as well as cancer treatment-related cardiac dysfunction (CTRCD) are needed to give oncologists data to support aggressive use of dexrazoxane in their patients.