Anthracycline-Associated Cardiotoxicity in Survivors of Childhood Cancer

Anthracycline chemotherapeutic agents are widely used to treat childhood cancers, helping to create an increasing population of childhood cancer survivors. Cardiac complications can occur years after exposure to anthracyclines and are a leading cause of noncancerous morbidity and mortality in this population. The mechanism of its cardiotoxicity is not completely known, although oxidative stress is believed to play a significant role. This pathway and other nonoxidative mechanisms are reviewed. Several risk factors such as age, dose, female gender, and concomitant radiation therapy are known, but the relative risks of many comorbidities such as diabetes and hypertension are not well studied. No standard, evidence-based guidelines for appropriate screening methods to detect cardiotoxicity exist. Periodic imaging with echocardiography or radionuclide angiography is appropriately recommended for long-term survivors but is of limited use during therapy. Biomarkers such as cardiac troponins and brain natriuretic peptides may aid in detecting cardiotoxicity. Studies investigating the use of agents such as angiotensinconverting enzyme (ACE)-inhibitors and beta-blockers to treat anthracycline cardiotoxicity have shown promise, but more data are needed. Structural analogs such as epirubicin were developed to minimize cardiotoxicity but have not sufficiently reduced it. Liposome-encapsulated anthracyclines have shown a considerable decrease of cardiotoxicity in adults without sacrificing efficacy, but the data related to children are sparse. The only agent proven to be cardioprotective is the iron chelator, dexrazoxane. Studies have shown that dexrazoxane is safe and significantly reduces the incidence of cardiotoxicity. Dexrazoxane should be considered for pediatric oncology protocols using anthracyclines that include longitudinal assessment.