Abstract
The older population is preferentially afflicted by cancer and is vulnerable to chemotherapy-related side effects including cardiotoxicity. Unfortunately, this high-risk group is underrepresented in clinical trials and as such there is little guidance for risk assessment and management. In this review, we focus on the commonly used chemotherapeutic agents and their deleterious cardiovascular effects, particularly in the elderly.
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Siegel R et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220–41.
Kendal WS. Dying with cancer. Cancer. 2008;112(6):1354–62.
Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339(13):900–5.
Cardinale D et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010;55(3):213–20. This study evaluated the effect of enalapril and carvedilol on left ventricular systolic function and cardiac outcomes in patients who developed anthracycline induced cardiomyopathy.
Du XL et al. Cardiac toxicity associated with anthracycline-containing chemotherapy in older women with breast cancer. Cancer. 2009;115(22):5296–308.
Pinder MC et al. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol. 2007;25(25):3808–15.
Hequet O et al. Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults. J Clin Oncol. 2004;22(10):1864–71.
Lotrionte M et al. Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity. Am J Cardiol. 2013;112(12):1980–4.
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin. Cancer. 2003;97(11):2869–79.
Nabhan C et al. Analysis of very elderly (≥80 years) non-hodgkin lymphoma: impact of functional status and co-morbidities on outcome. Br J Haematol. 2012;156(2):196–204.
van Dalen, E.C., et al., Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst Rev, 2010(3): p. Cd005006.
van Dalen, E.C., et al., Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev, 2011(6): p. Cd003917.
Fumoleau P et al. Long-term cardiac toxicity after adjuvant epirubicin-based chemotherapy in early breast cancer: French Adjuvant Study Group Results. Ann Oncol. 2006;17(1):85–92.
Ryberg M et al. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst. 2008;100(15):1058–67.
Yancy CW et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147–239.
Seicean S et al. Cardioprotective effect of beta-adrenoceptor blockade in patients with breast cancer undergoing chemotherapy: follow-up study of heart failure. Circ Heart Fail. 2013;6(3):420–6. This study showed that beta-blockers were cardioprotective in breast cancer patients receiving trastuzumab and anthracycline-based chemotherapy.
Todorova VK et al. Transcriptome profiling of peripheral blood cells identifies potential biomarkers for doxorubicin cardiotoxicity in a rat model. PLoS ONE. 2012;7(11):e48398.
Hensley ML et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27(1):127–45.
Russell SD et al. Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the National Surgical Adjuvant breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 clinical trials. J Clin Oncol. 2010;28(21):3416–21.
Spano J-P et al. Current targeted therapies in breast cancer: clinical applications in the elderly woman. Oncologist. 2011;16(8):1144–53.
Du XL et al. Cardiac risk associated with the receipt of anthracycline and trastuzumab in a large nationwide cohort of older women with breast cancer, 1998–2005. Med Oncol. 2011;28 Suppl 1:S80–90.
Chen J et al. Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol. 2012;60(24):2504–12.
Tarantini L et al. Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis. Ann Oncol. 2012;23(12):3058–63. This study showed that female breast cancer patients over the age of 60 had a higher incidence of trastuzumab-based cardiotoxicity compared to younger women.
Chavez-MacGregor M et al. Trastuzumab-related cardiotoxicity among older patients with breast cancer. J Clin Oncol. 2013;31(33):4222–8.
Serrano C et al. Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol. 2012;23(4):897–902. This study showed that elderly breast cancer patients with cardiovascular risk factors and over the age of 70 had a high incidence of trastuzumab-related cardiotoxicity.
Adamo V et al. The risk of toxicities from trastuzumab, alone or in combination, in an elderly breast cancer population. Oncology. 2014;86(1):16–21.
Baselga J et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–19. This study showed that there were no increased cardiotoxic effects when pertuzumab was added to trastuzumab and docetaxel chemotherapy in HER2-positive metastatic breast cancer patients.
Genentech, I., Herceptin (trastuzumab) prescribing information. 2014.
Schutz FA et al. Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. J Clin Oncol. 2012;30(8):871–7. This meta-analysis of 10 randomized controlled trials showed that there was an increased risk of fatal adverse events in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors.
Procopio G et al. Sorafenib tolerability in elderly patients with advanced renal cell carcinoma: results from a large pooled analysis. Br J Cancer. 2013;108(2):311–8. This meta-analysis showed that age does not impact drug-related adverse events in renal cell cancer patients treated with sorafenib.
Tsai HT et al. Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study. Ann Oncol. 2013;24(6):1574–9.
Scappaticci FA et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. 2007;99(16):1232–9.
Advani RH et al. Cardiac toxicity associated with bevacizumab (Avastin) in combination with CHOP chemotherapy for peripheral T cell lymphoma in ECOG 2404 trial. Leuk Lymphoma. 2012;53(4):718–20.
Choueiri TK et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol. 2011;29(6):632–8.
Kruzliak P, Kovacova G, Pechanova O. Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertension. Angiogenesis. 2013;16(2):289–95.
Atallah E et al. Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood. 2007;110(4):1233–7.
Marcolino MS et al. The duration of the use of imatinib mesylate is only weakly related to elevated BNP levels in chronic myeloid leukaemia patients. Hematol Oncol. 2011;29(3):124–30.
Estabragh ZR et al. A prospective evaluation of cardiac function in patients with chronic myeloid leukaemia treated with imatinib. Leuk Res. 2011;35(1):49–51.
Greil R et al. Combination therapy of lapatinib and Capecitabine for ErbB2-positive metastatic or locally advanced breast cancer: results from the Lapatinib Expanded Access Program (LEAP) in Central and Eastern Europe. Onkologie. 2011;34(5):233–8.
Polk A et al. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors. Cancer Treat Rev. 2013;39(8):974–84. This study systematically reviewed the manifestations of symptomatic cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine.
Kosmas C et al. Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol. 2008;134(1):75–82.
Jensen SA et al. Fluorouracil induces myocardial ischemia with increases of plasma brain natriuretic peptide and lactic acid but without dysfunction of left ventricle. J Clin Oncol. 2010;28(36):5280–6.
Brockstein BE et al. Cardiac and pulmonary toxicity in patients undergoing high-dose chemotherapy for lymphoma and breast cancer: prognostic factors. Bone Marrow Transplant. 2000;25(8):885–94.
Squibb, B.-M., Cytoxan (cyclophosphamide) package insert. 2005.
Haugnes HS et al. Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study. J Clin Oncol. 2010;28(30):4649–57.
Traish AM et al. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl. 2009;30(1):10–22.
Keating NL et al. Does comorbidity influence the risk of myocardial infarction or diabetes during androgen-deprivation therapy for prostate cancer? Eur Urol. 2013;64(1):159–66.
Hill BT et al. The non-relapse mortality rate for patients with diffuse large B-cell lymphoma is greater than relapse mortality 8 years after autologous stem cell transplantation and is significantly higher than mortality rates of population controls. Br J Haematol. 2011;152(5):561–9.
Stillwell EE et al. Retrospective outcome data for hematopoietic stem cell transplantation in patients with concurrent coronary artery disease. Biol Blood Marrow Trans. 2011;17(8):1182–6. This study showed that in cancer patients with or without pre-existing coronary artery disease, there was no significant difference in the treatment-related mortality, mortality at 1 year, and length of stay during hematopoietic stem cell transplantation.
Steuter JA et al. Factors affecting the development of atrial fibrillation and atrial flutter (AF/AFL) following autologous hematopoietic SCT (auto-HSCT). Bone Marrow Transplant. 2013;48(7):963–5.
Spina M et al. Modulated chemotherapy according to modified comprehensive geriatric assessment in 100 consecutive elderly patients with diffuse large B-cell lymphoma. Oncologist. 2012;17(6):838–46.
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Richard Steingart, Dipti Gupta, Frank Evans, and Nandini Yadav have no conflicts of interest.
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This article is part of the Topical Collection on Elderly and Heart Disease
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Gupta, D., Yadav, N., Evans, F. et al. Chemotherapy-Induced Cardiomyopathy in the Elderly. Curr Cardiovasc Risk Rep 8, 414 (2014). https://doi.org/10.1007/s12170-014-0414-5
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DOI: https://doi.org/10.1007/s12170-014-0414-5