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Heart 94:525-533 doi:10.1136/hrt.2007.136093
  • Education in Heart
  • Clinical pharmacology

Anthracycline associated cardiotoxicity in survivors of childhood cancer

  1. Steven E Lipshultz1,
  2. Jorge A Alvarez2,
  3. Rebecca E Scully2
  1. 1
    Department of Pediatrics, Leonard M Miller School of Medicine, University of Miami, Holtz Children’s Hospital of the University of Miami/Jackson Memorial Medical Center, and the University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida, USA
  2. 2
    Department of Pediatrics, Division of Clinical Research, University of Miami Miller School of Medicine, Miami, Florida, USA
  1. Steven E Lipshultz, MD, Department of Pediatrics, Leonard M Miller School of Medicine, University of Miami, Holtz Children’s Hospital of the University of Miami/Jackson Memorial Medical Center and The University of Miami Sylvester Comprehensive Cancer Center, PO Box 016820 (D820), Miami, FL 33101, USA; slipshultz{at}med.miami.edu

    The development of effective antineoplastic therapies for childhood cancer is a great success in modern medicine. Five year survival rates of children diagnosed with cancer in the USA and Western Europe in excess of 70% make long term survivors of childhood cancer a steadily increasing population. Although there is much to celebrate, new challenges lie ahead in treating the systemic sequelae of chemotherapy.1 Results from the Childhood Cancer Survivor Study (CCSS) showed that 30 years after treatment, the cumulative incidence of chronic health conditions in long term survivors reaches 73%, with a cumulative incidence of 42% for severe, disabling, or life threatening conditions or death.2 Severe conditions, that are significantly more common in childhood cancer survivors than in their siblings, include: major joint replacement (relative risk (RR) 54.0), congestive heart failure (RR 15.1), second malignant neoplasm (RR 14.8), severe cognitive dysfunction (RR 10.5), coronary artery disease (RR 10.4), cerebrovascular accident (RR 9.3), and renal failure (RR 8.9).2 Previous CCSS results found that patients who had survived at least 5 years after diagnosis had 10.8-fold increased rates of all cause mortality.3 The standardised mortality ratio for cardiac causes was 8.2 times higher than expected and the cumulative probability of cardiac death increased 15–25 years after cancer diagnosis. A similar study in a large Nordic cohort documented a standardised mortality ratio of 5.8 for cardiac death and elevated rates of sudden, presumed arrhythmic, deaths.4

    Chief among adverse late effects is the cardiovascular toxicity of anthracyclines.511 Unfortunately, despite well documented dose related toxicity, the superior disease-free survival rates of regimens including anthracyclines leave limited viable treatment alternatives and the majority of long term paediatric cancer survivors in the Pediatric Oncology Group received an anthracycline during treatment.12

    NATURAL HISTORY OF ANTHRACYCLINE CARDIOTOXICITY

    Mechanism of cardiotoxicity

    Several cytotoxic biochemical changes follow anthracycline exposure in …