Anthracycline-related cardiac toxicity

Late complications related to anthracycline injury may include subclinical left ventricular dysfunction, cardiomyopathy, and congestive heart failure.[27]

Increased risk of doxorubicin-related cardiomyopathy is associated with female sex, treatment with cumulative doses of 250 mg/m2 or higher, younger age at time of exposure, and increased time from exposure.[37]

Prevention or amelioration of anthracycline-induced cardiomyopathy is important because anthracyclines are required in cancer therapy in more than one-half of children with newly diagnosed cancer.[38,39]

Dexrazoxane (a bisdioxopiperazine compound that readily enters cells and is subsequently hydrolyzed to form a chelating agent) has been shown to prevent heart damage in adults and children treated with anthracyclines.[40] Studies suggest that dexrazoxane is safe and does not interfere with chemotherapeutic efficacy. Dexrazoxane has been associated with increased hematologic toxicity and typhlitis in children with Hodgkin lymphoma receiving ABVE-PC chemotherapy.[41]

A number of trials have studied the risk of subsequent neoplasms following dexrazoxane administration, and none has found a significant association with subsequent neoplasms.[42,43] However, one study found a borderline statistical increase in subsequent neoplasms in patients randomly assigned to receive dexrazoxane. This increase was attributed to the administration of three topoisomerase inhibitors (doxorubicin, etoposide, and dexrazoxane) within 2 to 3 hours of each other.[44]

Studies of cancer survivors treated with anthracyclines have not demonstrated the benefit of enalapril in preventing progressive cardiac toxicity.[45,46]