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Cardiotoxicity of Cancer Chemotherapy

Implications for Children

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Abstract

Many children and adolescents with cancer receive chemotherapeutic agents that are cardiotoxic. Thus, while survival rates in this population have improved for some cancers, many survivors may experience acute or chronic cardiovascular complications that can impair their quality of life years after treatment. In addition, cardiac complications of treatment lead to reductions in dose and duration of chemotherapy regimens, potentially compromising clinical efficacy.

Anthracyclines are well known for their cardiotoxicity, and alkylating agents, such as cyclophosphamide, ifosfamide, cisplatin, busulfan, and mitomycin, have also been associated with cardiotoxicity. Other agents with cardiac effects include vinca alkaloids, fluorouracil, cytarabine, amsacrine, and asparaginase and the newer agents, paclitaxel, trastuzumab, etoposide, and teniposide. The heart is relatively vulnerable to oxidative injuries from oxygen radicals generated by chemotherapy.

The cardiac effects of these drugs include asymptomatic electrocardiographic abnormalities, blood pressure changes, arrhythmias, myocarditis, pericarditis, cardiac tamponade, acute myocardial infarction, cardiac failure, shock, and long-term cardiomyopathy. These effects may occur during or immediately after treatment or may not be apparent until months or years after treatment.

Mild myocardiocyte injury from chemotherapy may be of more concern in children than in adults because of the need for subsequent cardiac growth to match somatic growth and because survival is longer in children. Primary prevention is therefore important. Patients should be educated about the cardiotoxic risks of treatment and the need for long-term cardiac monitoring before chemotherapy is begun. Cardiotoxicity may be prevented by screening for risk factors, monitoring for signs and symptoms during chemotherapy, and continuing follow-up that may include electrocardiographic and echocardiographic studies, angiography, and measurements of biochemical markers of myocardial injury.

Secondary prevention should aim to minimize progression of left ventricular dysfunction to overt heart failure. Approaches include altering the dose, schedule, or approach to drug delivery; using analogs or new formulations with fewer or milder cardiotoxic effects; using cardioprotectants and agents that reduce oxidative stress during chemotherapy; correcting for metabolic derangements caused by chemotherapy that can potentiate the cardiotoxic effects of the drug; and cardiac monitoring during and after cancer therapy. Avoiding additional cardiotoxic regimens is also important in managing these patients. Treating the adverse cardiac effects of chemotherapy will usually be dependent on symptoms or will depend on the anticipated cardiovascular effects of each regimen. Treatments include diuresis, afterload reduction, β-adrenoceptor antagonists, and improving myocardial contractility.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgments

This review was supported in part by the National Institutes of Health, Bethesda, MD (CA-79060, HL59837, HR96041, CA68484, HL53392, HL78522, HL72705), Lance Armstrong Foundation, and the Children’s Cardiomyopathy Foundation. Dr Lipshultz has been a consultant for Chiron and has received investigator-initiated research grants from Chiron, Pfizer, and Roche Diagnostics.

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Authors and Affiliations

  1. Division of Pediatric Cardiology, University of Rochester Medical Center and Golisano Children’s Hospital at Strong, Rochester, New York, USA

    Valeriano C. Simbre II, Sarah A. Duffy, Gul H. Dadlani &  Steven E. Lipshultz

  2. Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA

    Valeriano C. Simbre II, Gul H. Dadlani, Trade L. Miller &  Steven E. Lipshultz

  3. Department of Pediatrics, University of Miami Miller School of Medicine, Medical Campus MCCD-D820, 1601 NW 12th Avenue, 9th Floor, Miami, FL, 33136, USA

    Sarah A. Duffy, Trade L. Miller &  Steven E. Lipshultz

  4. Holtz Children’s Hospital of the University of Miami/Jackson Memorial Medical Center, Batchelor Children’s Research Institute, Mailman Center for Child Development, USA

    Sarah A. Duffy, Trade L. Miller &  Steven E. Lipshultz

  5. Sylvester Comprehensive Cancer Center, Miami, Florida, USA

    Sarah A. Duffy, Trade L. Miller &  Steven E. Lipshultz

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  1. Valeriano C. Simbre II
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Correspondence to Steven E. Lipshultz.

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Simbre, V.C., Duffy, S.A., Dadlani, G.H. et al. Cardiotoxicity of Cancer Chemotherapy. Pediatr-Drugs 7, 187–202 (2005). https://doi.org/10.2165/00148581-200507030-00005

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