Prevention of Chemotherapy Induced Cardiomyopathy
- 1.2k Downloads
Purpose of Review
Cardiomyopathy is a significant complication of various cancer treatments and has been best studied in patients receiving anthracyclines and trastuzumab. This paper evaluates strategies to prevent chemotherapy-induced cardiotoxicity.
Increasing cumulative anthracycline dose, use of ≥2 cardiotoxic therapies, extremes of age, and pre-existing cardiovascular risk factors, or established cardiovascular disease, heighten the risk of developing chemotherapy-induced cardiomyopathy. Continuous rather than bolus anthracycline infusions, liposomal doxorubicin, or concomitant dexrazoxane reduces chemotherapy-induced cardiotoxicity. Treatment with neurohormonal antagonists or statins and exercise training during chemotherapy are promising, but as yet unproven, cardioprotective strategies.
Identification of high-risk patients and optimization of their underlying cardiovascular risk factors/disease are essential to prevent cardiotoxicity. In patients requiring high-dose anthracyclines, continuous infusions, liposomal doxorubicin, or dexrazoxane should be considered to mitigate cardiotoxicity. Current data do not support the routine use of neurohormonal antagonists or statins as cardioprotective agents in patients treated with cardiotoxic chemotherapies.
KeywordsCardiotoxicity Chemotherapy-induced cardiomyopathy Anthracyclines Cardio protectant Dexrazoxane Neurohormonal antagonists
Compliance with Ethical Standards
Conflict of Interest
David L. Payne, BA and Anju Nohria, MD declare no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 8.Bria E, Cuppone F, Fornier M, Nistico C, Carlini P, Milella M, et al. Cardiotoxicity and incidence of brain metastases after adjuvant trastuzumab for early breast cancer: the dark side of the moon? A meta-analysis of the randomized trials. Breast Cancer Res Tr. 2008;109:231–9. doi: 10.1007/s10549-007-9663-z.CrossRefGoogle Scholar
- 12.Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systemic review and meta-analysis of randomized controlled trials. BMC Cancer. 2010;10:337. doi: 10.1186/1471-2407-10-337.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.O’Brien ME, Wigler N, Inbar MC, Rosso R, Grischke E, Santoro A, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX™/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15:440–9. doi: 10.1093/annonc.mdh097.CrossRefPubMedGoogle Scholar
- 15.Swain SM, Whaley FS, Gerber MC, Ewer MS, Bianchine JR, Gams RA. Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy. J Clin Oncol. 1997;15:1333–40. doi: 10.1200/JCO.19184.108.40.2063.CrossRefPubMedGoogle Scholar
- 16.Shaikh F, Dupuis LL, Alexander S, Gupta A, Mertens L, Nathan PC. Cardioprotection and second malignant neoplasms associated with dexrazoxane in children receiving anthracycline chemotherapy: a systematic review and meta-analysis. J Natl Cancer I 2016:108. doi: 10.1093/inci/djv357.
- 17.•• Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American society of clinical oncology clinical practice guideline. J Clin Oncol. 2017;35:893–911. doi: 10.1200/JCO.2016.70.5400. This paper contains the 2016 guidelines from the American Society of Clinical Oncology regarding the prevention and monitoring of cardiac dysfunction in survivors of adult cancer. CrossRefPubMedGoogle Scholar
- 21.• Bosch X, Rovira M, Sitges M, Domènech A, Ortiz-Pérez JT, de Caralt TM, et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013;61:2355–62. doi: 10.1016/j.jacc.2013.02.072. Patients receiving concomitant enalapril and carvedilol had a smaller reduction in left ventricular ejection fraction compared to placebo in patients receiving high dose anthracycline therapy for hematologic malignancies. Furthermore, enalapril and carvedilol significantly reduced the combined end-point of heart failure and death relative to placebo. CrossRefPubMedGoogle Scholar
- 22.• Pituskin E, Mackey JR, Koshman S, Jassal D, Pitz M, Haykowsky MJ, et al. Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101–breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity. J Clin Oncol. 2016;35:870–7. doi: 10.1200/JCO.2016.68.7830. In this study, pre-treatment with both bisoprolol and perindopril attenuated a decline in left ventricular ejection fraction in a group of HER2+ breast cancer patients undergoing treatment with trastuzumab. CrossRefPubMedGoogle Scholar
- 23.• Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016;37:1671–80. doi: 10.1093/eurheartj/ehw022. In this study, cardioprotective treatment with candesartan attenuated a decline in left ventricular ejection fraction in HER2+ breast cancer patients undergoing anthacycline-containing chemotherapy. Metoprolol cardioprotective treatment did not prevent a decline in left ventricular ejection fraction. CrossRefPubMedPubMedCentralGoogle Scholar
- 25.• Akpek M, Ozdogru I, Sahin O, Inanc M, Dogan A, Yazici C, et al. Protective effects of spironolactone against anthracycline-induced cardiomyopathy. Eur J Heart Fail. 2015;17:81–9. doi: 10.1002/ejhf.196. Concomitant spironolactone treatment was associated with preservation of systolic and diastolic heart function in breast cancer patients undergoing anthracycline-containing chemotherapy. CrossRefPubMedGoogle Scholar