We review the cardiotoxic chemotherapeutic agents, the clinical and subclinical presentations and progression of their cardiotoxicity, and the management of the subsequent cardiovascular disease in survivors of childhood cancer. We discuss various preventive measures, especially the cardioprotectant, dexrazoxane, whose use with anthracycline chemotherapy, including doxorubicin, is based on strong evidence. Most treatment recommendations for this unique population are based on expert opinion, not on empirical evidence.
As patients with childhood cancers live longer, morbidity from the cardiac side effects of chemotherapy is increasing. Treatment-related cardiac damage is irreversible and often progressive. It is imperative that such damage be prevented with strategies such as limiting the cumulative anthracycline dose, the use of anthracycline structural analogues and the use of cardioprotective agents.
A deeper understanding of the mechanisms of their cardiotoxicity reveals that there is no ‘safe’ dose of anthracyclines. However, certain risk factors, such as higher lifetime anthracycline cumulative doses, higher anthracycline dose rates, female sex, longer follow-up, younger age at anthracycline treatment and cardiac irradiation, are associated with more severe cardiotoxicity. We advocate the use of dexrazoxane to limit the cardiotoxic effects of anthracycline chemotherapy.
aDivision of Pediatric Cardiology, Children's Hospital of Michigan, Detroit
bDivision of Pediatric Cardiology, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis
cDivision of Pediatric Hematology-Oncology, Children's Hospital of Michigan
dDepartment of Pediatrics, Wayne State University School of Medicine
eKarmanos Cancer Institute, Detroit, Michigan, USA
Correspondence to Steven E. Lipshultz, MD, Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, 3901 Beaubien Boulevard, Pediatric Administration-T121A, Detroit, MI 48201, USA. Tel: +1 313 745 5870; fax: +1 313 993 0390; e-mail: firstname.lastname@example.org