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Cardiotoxicity of anticancer treatments: what the cardiologist needs to know

Nature Reviews Cardiology volume 7, pages 564–575 (2010)Cite this article

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Abstract

Cardiotoxicity of anticancer treatments has become an increasingly important clinical problem faced by cardiologists. Left ventricular systolic dysfunction and heart failure generate the most concern, but clinical features and prognosis vary considerably depending on the causative agent. Anthracycline-related cardiomyopathy differs fundamentally from effects associated with newer targeted agents, such as trastuzumab. Other forms of cardiovascular disease that occur as a result of cancer treatment include hypertension, thromboembolic disease, pericardial disease, arrhythmia, and myocardial ischemia. The approach to cardiovascular disease in patients with cancer is often different from that in the general population, not only because of distinct underlying mechanisms and clinical features of their heart disease, but also because of the potential ongoing need for additional cancer treatment as well as the altered duration of anticipated survival. In an effort to maximize both quality of life and survival, cardiologists and oncologists should collaborate with the aim of balancing the risks of cardiotoxicity with the benefits of oncologic therapy.

Key Points

  • The effects of anticancer treatment are implicated in an array of cardiovascular conditions

  • Anthracyclines are highly effective for the treatment of cancer, but cause an irreversible cardiomyopathy that is related to cumulative dose, and carries a poor prognosis

  • Novel targeted chemotherapeutic agents, such as trastuzumab, can cause left ventricular dysfunction that is fundamentally different from that caused by anthracyclines and follows a more benign course

  • Therapeutic radiation that involves cardiac structures can lead to pericardial disease, restrictive cardiomyopathy, accelerated coronary artery disease, and valvular heart disease

  • Cardiologists and oncologists must work in close collaboration to assess the risks associated with anticancer treatments that potentially have cardiotoxic effects, and to optimize patient outcomes

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Figure 1: Incidence of heart failure following doxorubicin and trastuzumab therapy.

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References

  1. Farooq, M. U., Bhatt, A. & Patel, M. Neurotoxic and cardiotoxic effects of cocaine and ethanol. J. Med. Toxicol. 5, 134–138 (2009).

    PubMed  PubMed Central  Google Scholar 

  2. Klatsky, A. L. Alcohol and cardiovascular diseases: a historical overview. Ann. NY Acad. Sci. 957, 7–15 (2002).

    PubMed  Google Scholar 

  3. American Cancer Society Cancer Facts & Figures 2010 [online], (2010).

  4. National Cancer Institute SEER Cancer Statistics Review 1975–2006, Table 1.21 [online], (2009).

  5. Gottlieb, J., Lefrak, E., O'Bryan, R. & Burgess, M. Fatal adriamycin cardiomyopathy (CMY): prevention by dose limitation [abstract]. Proc. Am. Assoc. Cancer Res. 14, 88 (1973).

    Google Scholar 

  6. van Halteren, H. K., Liem, A. H. & Planting, A. S. Myocardial ischemia as a result of treatment with capecitabine [Dutch]. Ned. Tijdschr. Geneeskd. 151, 1469–1473 (2007).

    CAS  PubMed  Google Scholar 

  7. Albini, A. et al. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J. Natl Cancer Inst. 102, 14–25 (2009).

    PubMed  Google Scholar 

  8. Ewer, M. S. & Yeh, E. T. (Eds) Cancer and the Heart (BC Decker, Hamilton, 2006).

    Google Scholar 

  9. Ewer, S. M. & Ewer, M. S. Cardiotoxicity profile of trastuzumab. Drug Saf. 31, 459–467 (2008).

    CAS  PubMed  Google Scholar 

  10. Ewer, M. S. & Lenihan, D. J. Left ventricular ejection fraction and cardiotoxicity: is our ear really to the ground? J. Clin. Oncol. 26, 1201–1203 (2008).

    PubMed  Google Scholar 

  11. Lefrak, E. A., Pitha, J., Rosenheim, S. & Gottlieb, J. A. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 32, 302–314 (1973).

    CAS  PubMed  Google Scholar 

  12. Ewer, M. S. & Lippman, S. M. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J. Clin. Oncol. 23, 2900–2902 (2005).

    CAS  PubMed  Google Scholar 

  13. Tan-Chiu, E. et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J. Clin. Oncol. 23, 7811–7819 (2005).

    CAS  PubMed  Google Scholar 

  14. Suter, T. M. et al. Trastuzumab-associated cardiac adverse effects in the Herceptin Adjuvant Trial. J. Clin. Oncol. 25, 3859–3865 (2007).

    CAS  PubMed  Google Scholar 

  15. Perez, E. A. et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J. Clin. Oncol. 26, 1231–1238 (2008).

    CAS  PubMed  Google Scholar 

  16. Slamon, D. et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study [abstract 62]. San Antonio Breast Cancer Symposium 2009.

  17. Joensuu, H. et al. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J. Clin. Oncol. 27, 5685–5692 (2009).

    CAS  PubMed  Google Scholar 

  18. Ewer, M. S. et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J. Clin. Oncol. 23, 7820–7826 (2005).

    CAS  PubMed  Google Scholar 

  19. Telli, M. L., Hunt, S. A., Carlson, R. W. & Guardino, A. E. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J. Clin. Oncol. 25, 3525–3533 (2007).

    CAS  PubMed  Google Scholar 

  20. Guglin, M., Hartlage, G., Reynolds, C., Chen, R. & Patel, V. Trastuzumab-induced cardiomyopathy: not as benign as it looks? A retrospective study. J. Card. Fail. 15, 651–657 (2009).

    CAS  PubMed  Google Scholar 

  21. Ewer, M. S. & Tan-Chiu, E. Reversibility of trastuzumab cardiotoxicity: is the concept alive and well? J. Clin. Oncol. 25, 5532–5533 (2007).

    PubMed  Google Scholar 

  22. Chaires, J. B. Biophysical chemistry of daunomycin-DNA interaction. Biophys. Chem. 35, 191–202 (1990).

    CAS  PubMed  Google Scholar 

  23. Doroshow, J. H. Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res. 43, 460–472 (1983).

    CAS  PubMed  Google Scholar 

  24. Kang, Y. J., Chen, Y. & Epstein, P. N. Suppression of doxorubicin cardiotoxicity by overexpression of catalase in the heart of transgenic mice. J. Biol. Chem. 271, 12610–12616 (1996).

    CAS  PubMed  Google Scholar 

  25. Dodd, D. A. et al. Doxorubicin cardiomyopathy is associated with a decrease in calcium release channel of the sarcoplasmic reticulum in a chronic rabbit model. J. Clin. Invest. 91, 1697–1705 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Lim, C. C. et al. Anthracyclines induce calpain-dependent titin proteolysis and necrosis in cardiomyocytes. J. Biol. Chem. 279, 8290–8299 (2004).

    CAS  PubMed  Google Scholar 

  27. Von Hoff, D. D. et al. Risk factors for doxorubicin-induced congestive heart failure. Ann. Intern. Med. 91, 710–717 (1979).

    CAS  PubMed  Google Scholar 

  28. Billingham, M. E., Mason, J. W., Bristow, M. R. & Daniels, J. R. Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat. Rep. 62, 865–872 (1978).

    CAS  PubMed  Google Scholar 

  29. Billingham, M. & Bristow, M. Evaluation of anthracycline cardiotoxicity: predictive ability and functional correlation of endomyocardial biopsy. Cancer Treat. Symp. 3, 71–76 (1984).

    Google Scholar 

  30. Mackay, B., Ewer, M. S., Carrasco, C. H. & Benjamin, R. S. Assessment of anthracycline cardiomyopathy by endomyocardial biopsy. Ultrastruct. Pathol. 18, 203–211 (1994).

    CAS  PubMed  Google Scholar 

  31. Cardinale, A. et al. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann. Oncol. 13, 710–715 (2002).

    CAS  PubMed  Google Scholar 

  32. Ewer, M. & Benjamin, R. Formulae for predicting the likelihood of developing congestive heart failure following anthracycline chemotherapy: added evidence for early cardiotoxicity [abstract]. J. Card. Fail. 11 (Suppl.), S159 (2005).

    Google Scholar 

  33. Swain, S. M., Whaley, F. S. & Ewer, M. S. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97, 2869–2879 (2003).

    CAS  PubMed  Google Scholar 

  34. Rao, S. et al. Matuzumab plus epirubicin, cisplatin and capecitabine (ECX) compared with epirubicin, cisplatin and capecitabine alone as first-line treatment in patients with advanced oesophago-gastric cancer: a randomised, multicentre open-label phase II study. Ann. Oncol. doi:10.1093/annonc/mdq247.

    CAS  PubMed  Google Scholar 

  35. Bedano, P. M., Brames, M. J., Williams, S. D., Juliar, B. E. & Einhorn, L. H. Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors. J. Clin. Oncol. 24, 5403–5407 (2006).

    CAS  PubMed  Google Scholar 

  36. Ryberg, M. et al. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J. Natl Cancer Inst. 100, 1058–1067 (2008).

    CAS  PubMed  Google Scholar 

  37. Jain, K. K. et al. A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer. J. Clin. Oncol. 3, 818–826 (1985).

    CAS  PubMed  Google Scholar 

  38. Bonneterre, J. et al. Long-term cardiac follow-up in relapse-free patients after six courses of fluorouracil, epirubicin, and cyclophosphamide, with either 50 or 100 mg of epirubicin, as adjuvant therapy for node-positive breast cancer: French adjuvant study group. J. Clin. Oncol. 22, 3070–3079 (2004).

    CAS  PubMed  Google Scholar 

  39. van Dalen, E. C., Michiels, E. M., Caron, H. N. & Kremer, L. C. Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database of Systematic Reviews, Issue 4. Art. No.:CD005006. doi:10.1002/14651858.CD005006.pub4 (2006).

  40. Ewer, M. S. et al. Cardiac safety of liposomal anthracyclines. Semin. Oncol. 31 (Suppl. 13), 161–181 (2004).

    CAS  PubMed  Google Scholar 

  41. Calabresi, L. et al. High-density lipoproteins protect isolated rat hearts from ischemia-reperfusion injury by reducing cardiac tumor necrosis factor-alpha content and enhancing prostaglandin release. Circ. Res. 92, 330–337 (2003).

    CAS  PubMed  Google Scholar 

  42. Valero, V. et al. Phase II trial of liposome-encapsulated doxorubicin, cyclophosphamide, and fluorouracil as first-line therapy in patients with metastatic breast cancer. J. Clin. Oncol. 17, 1425–1434 (1999).

    CAS  PubMed  Google Scholar 

  43. Rahman, A. M., Yusuf, S. W. & Ewer, M. S. Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int. J. Nanomedicine 2, 567–583 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Lotrionte, M. et al. Appraising cardiotoxicity associated with liposomal doxorubicin by means of tissue Doppler echocardiography end-points: rationale and design of the LITE (Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation) randomized pilot study. Int. J. Cardiol. 135, 72–77 (2009).

    PubMed  Google Scholar 

  45. Sparano, J. A. et al. Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J. Clin. Oncol. 27, 4522–4529 (2009).

    CAS  PubMed  Google Scholar 

  46. Orlowski, R. Z. et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J. Clin. Oncol. 25, 3892–3901 (2007).

    CAS  PubMed  Google Scholar 

  47. Minow, R. A., Benjamin, R. S., Lee, E. T. & Gottlieb, J. A. Adriamycin cardiomyopathy—risk factors. Cancer 39, 1397–1402 (1977).

    CAS  PubMed  Google Scholar 

  48. Ewer, M. S. et al. Cardiac safety guidelines for the adjuvant use of trastuzumab (Herceptin) in HER2-positive early breast cancer. Presented at the 10th International St Gallen Conference: Primary Therapy of Early Breast Cancer.

  49. Jones, A. L. et al. Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring. Br. J. Cancer 100, 684–692 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Carver, J. R. et al. for the ASCO Cancer Survivorship Expert Panel. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J. Clin. Oncol. 25, 3991–4008 (2007).

    CAS  PubMed  Google Scholar 

  51. Cardinale, D. et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J. Am. Coll. Cardiol. 55, 213–220 (2010).

    CAS  PubMed  Google Scholar 

  52. Cardinale, D. et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 109, 2749–2754 (2004).

    CAS  PubMed  Google Scholar 

  53. Auner, H. W. et al. Prolonged monitoring of troponin T for the detection of anthracycline cardiotoxicity in adults with hematological malignancies. Ann. Hematol. 82, 218–222 (2003).

    CAS  PubMed  Google Scholar 

  54. Sandri, M. T. et al. N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction? Clin. Chem. 51, 1405–1410 (2005).

    CAS  PubMed  Google Scholar 

  55. Nousiainen, T. et al. Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction. J. Intern. Med. 251, 228–234 (2002).

    CAS  PubMed  Google Scholar 

  56. Suzuki, T. et al. Elevated B-type natriuretic peptide levels after anthracycline administration. Am. Heart J. 136, 362–363 (1998).

    CAS  PubMed  Google Scholar 

  57. Vogelsang, T. W., Jensen, R. J., Hesse, B. & Kjaer, A. BNP cannot replace gated equilibrium radionuclide ventriculography in monitoring of anthracycline-induced cardiotoxity. Int. J. Cardiol. 124, 193–197 (2008).

    PubMed  Google Scholar 

  58. Feola, M. et al. Cardiotoxicity after anthracycline chemotherapy in breast carcinoma: effects on left ventricular ejection fraction, troponin I and brain natriuretic peptide. Int. J. Cardiol. doi:10.1016/j.ijcard.2009.09.564.

    PubMed  Google Scholar 

  59. Legha, S. S. et al. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann. Intern. Med. 96, 133–139 (1982).

    CAS  PubMed  Google Scholar 

  60. Benjamin, R. in Cancer Treatment and the Heart (The Johns Hopkins Series in Hematology/Oncology) (eds Muggia, F. M. & Speyer, J. L.) 278–285 (Johns Hopkins University Press, Baltimore, 1992).

    Google Scholar 

  61. Ewer, M. S., Jaffe, N., Ried, H., Zietz, H. A. & Benjamin, R. S. Doxorubicin cardiotoxicity in children: comparison of a consecutive divided daily dose administration schedule with single dose (rapid) infusion administration. Med. Pediatr. Oncol. 31, 512–515 (1998).

    CAS  PubMed  Google Scholar 

  62. Swain, S. M. Adult multicenter trials using dexrazoxane to protect against cardiac toxicity. Semin. Oncol. 25 (Suppl. 10), 43–47 (1998).

    CAS  PubMed  Google Scholar 

  63. Swain, S. M. et al. Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing chemotherapy. J. Clin. Oncol. 15, 1333–1340 (1997).

    CAS  PubMed  Google Scholar 

  64. Swain, S. et al. Cardioprotection with dexrazoxane for doxorubicin-containing chemotherapy in advanced breast cancer. J. Clin. Oncol. 15, 1318–1332 (1997).

    CAS  PubMed  Google Scholar 

  65. Speyer, J. L. et al. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer. N. Engl. J.Med. 319, 745–752 (1988).

    CAS  PubMed  Google Scholar 

  66. Benjamin, R. S. et al. Evaluation of mitoxantrone cardiac toxicity by nuclear angiography and endomyocardial biopsy: an update. Invest. New Drugs 3, 117–121 (1985).

    CAS  PubMed  Google Scholar 

  67. Posner, L. E., Kukart, G., Goldberg, J., Bernstein, T. & Cartwright, K. Mitoxantrone: an overview of safety and toxicity. Invest. New Drugs 3, 123–132 (1985).

    CAS  PubMed  Google Scholar 

  68. Katayama, M. et al. Fulminant fatal cardiotoxicity following cyclophosphamide therapy. J. Cardiol. 54, 330–334 (2009).

    PubMed  Google Scholar 

  69. Dow, E., Schulman, H. & Agura, E. Cyclophosphamide cardiac injury mimicking acute myocardial infarction. Bone Marrow Transplant. 12, 169–172 (1993).

    CAS  PubMed  Google Scholar 

  70. Zhao, Y. Y. et al. Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J. Biol. Chem. 273, 10261–10269 (1998).

    CAS  PubMed  Google Scholar 

  71. Crone, S. A. et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat. Med. 8, 459–465 (2002).

    CAS  PubMed  Google Scholar 

  72. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001).

    CAS  PubMed  Google Scholar 

  73. Bria, E. et al. Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues. Expert Opin. Biol. Ther. 8, 1963–1971 (2008).

    CAS  PubMed  Google Scholar 

  74. Ewer, M. S., Gibbs, H., Swafford, J. & Benjamin, R. Cardiotoxicity in patients receiving trastuzumab (Herceptin): primary toxicity, synergistic or sequential stress, or surveillance artifact? Semin. Oncol. 26, 96–101 (1999).

    CAS  PubMed  Google Scholar 

  75. Mann, D. L. Mechanisms and models in heart failure: a combinatorial approach. Circulation 100, 999–1008 (1999).

    CAS  PubMed  Google Scholar 

  76. de Korte, M. A. et al. 111Indium-trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: a clue to uncover the mechanisms of trastuzumab-related cardiotoxicity. Eur. J. Cancer 43, 2046–2051 (2007).

    CAS  PubMed  Google Scholar 

  77. Force, T., Krause, D. S. & Van Etten, R. A. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat. Rev. Cancer 7, 332–344 (2007).

    CAS  PubMed  Google Scholar 

  78. Chu, T. F. et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370, 2011–2019 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Di Lorenzo, G. et al. Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis. Ann. Oncol. 20, 1535–1542 (2009).

    CAS  PubMed  Google Scholar 

  80. Hunt, S. A. et al. 2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J. Am. Coll. Cardiol. 53, e1–e90 (2009).

    PubMed  Google Scholar 

  81. Perez, E. A. et al. Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin. Proc. 83, 679–686 (2008).

    PubMed  Google Scholar 

  82. Kerkelä, R. et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat. Med. 12, 908–916 (2006).

    PubMed  Google Scholar 

  83. Atallah, E., Durand, J. B., Kantarjian, H. & Cortes, J. Congestive heart failure is a rare event in patients receiving imitinib therapy. Blood 110, 1233–1237 (2007).

    CAS  PubMed  Google Scholar 

  84. Kosmas, C. et al. Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J. Cancer Res. Clin. Oncol. 134, 75–82 (2008).

    CAS  PubMed  Google Scholar 

  85. Sugrue, M. M. et al. Serious arterial thromboembolic events (sATE) in patients (pts) with metastatic colorectal cancer (mCRC) treated with bevacizumab (BV): results from the BRiTE registry [abstract]. J. Clin. Oncol. 25, 4136 (2007).

    Google Scholar 

  86. Scappaticci, F. A. et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J. Natl Cancer Inst. 99, 1232–1239 (2007).

    PubMed  Google Scholar 

  87. Kazunori, O. et al. Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia. Ann. Intern. Med. 133, 881–885 (2001).

    Google Scholar 

  88. Rowinsky, E. K. et al. Cardiac disturbances during the administration of taxol. J. Clin. Oncol. 9, 1704–1712 (1991).

    CAS  PubMed  Google Scholar 

  89. Pande, A., Lombardo, J., Spangenthal, E. & Javle, M. Hypertension secondary to anti-angiogenic therapy: experience with bevacizumab. Anticancer Res. 27, 3465–3470 (2007).

    CAS  PubMed  Google Scholar 

  90. Ratain, M. J. et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 25, 2505–2512 (2006).

    Google Scholar 

  91. Burstein, H. J. et al. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J. Clin. Oncol. 26, 1810–1816 (2008).

    CAS  PubMed  Google Scholar 

  92. Shord, S. S., Bressler, L. R., Tierney, L. A., Cuellar, S. & George, A. Understanding and managing the possible adverse effects associated with bevacizumab. Am. J. Health Syst. Pharm. 66, 999–1013 (2009).

    CAS  PubMed  Google Scholar 

  93. Yeh, E. T. & Bickford, C. L. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis and management. J. Am. Coll. Cardiol. 53, 2231–2247 (2009).

    CAS  PubMed  Google Scholar 

  94. Palumbo, A. et al. for the International Myeloma Working Group. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 22, 414–423 (2008).

    CAS  PubMed  Google Scholar 

  95. Deitcher, S. R. & Gomes, M. P. The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma: a systematic review. Cancer 101, 439–449 (2004).

    PubMed  Google Scholar 

  96. Ewer, M. S. & Glück, S. A woman's heart: the impact of adjuvant endocrine therapy on cardiovascular health. Cancer 115, 1813–1826 (2008).

    Google Scholar 

  97. Thürlimann, B. et al. for the Breast International Group (BIG) 1-98 collaborative Group. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N. Engl. J. Med. 353, 2747–2757 (2005).

    PubMed  Google Scholar 

  98. Cardinale, D. et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114, 2474–2481 (2006).

    CAS  PubMed  Google Scholar 

  99. Kalay, N. et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J. Am. Coll. Cardiol. 48, 2258–2262 (2006).

    CAS  PubMed  Google Scholar 

  100. Mann, D. L. & Bristow, M. R. Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation 111, 2837–2849 (2005).

    PubMed  Google Scholar 

  101. Hancock, S. L., Tucker, M. A. & Hoppe, R. T Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. JAMA 270, 1949–1955 (1993).

    CAS  PubMed  Google Scholar 

  102. Mulrooney, D. A. et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339, b4606 (2009).

    PubMed  PubMed Central  Google Scholar 

  103. Tukenova, M. et al. Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J. Clin. Oncol. 28, 1308–1315 (2010).

    PubMed  Google Scholar 

  104. Darby, S. C., McGale, P., Taylor, C. W. & Peto, R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol. 6, 557–565 (2005).

    PubMed  Google Scholar 

  105. Spodick, D. H. in Heart Disease: a Textbook of Cardiovascular Medicine 6th edn (eds Braunwald, E., Zipes, D. P. & Libby, P.) 1823–1876 (W. B. Saunders Company, Philadelphia, 2001).

    Google Scholar 

  106. Schultz-Hector, S. Radiation-induced heart disease: review of experimental data on dose response and pathogenesis. Int. J. Radiat. Biol. 61, 149–160 (1992).

    CAS  PubMed  Google Scholar 

  107. Maisch, B. et al. Guidelines on the diagnosis and management of pericardial diseases executive summary; the Task Force on the diagnosis and management of pericardial diseases of the European Society of Cardiology. Eur. Heart J. 25, 587–610 (2004).

    PubMed  Google Scholar 

  108. Brosius, F. C. 3rd,, Waller, B. F. & Roberts, W. C. Radiation heart disease. Analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart. Am. J. Med. 70, 519–530 (1981).

    PubMed  Google Scholar 

  109. Joensuu, H. Dyslipidemia interacts with radiation. Recent Results Cancer Res. 130, 157–171 (1993).

    CAS  PubMed  Google Scholar 

  110. McEniery, P. T., Dorosti, K., Schiavone, W. A., Pedrick, P. J. & Sheldon, W. C. Clinical and angiographic features of coronary artery disease after chest irradiation. Am. J. Cardiol. 60, 1020–1024 (1987).

    CAS  PubMed  Google Scholar 

  111. Adams, M. J. et al. Cardiovascular status in long-term survivors of Hodgkin's disease treated with chest radiation. J. Clin. Oncol. 22, 3139–3148 (2004).

    PubMed  Google Scholar 

  112. Steinherz, L. J., Steinherz, P. G., Tan, C. T., Heller, G. & Murphy, M. L. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 266, 1672–1677 (1991).

    CAS  PubMed  Google Scholar 

  113. Hershman, D. L. et al. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma. J. Clin. Oncol. 26, 3159–3165 (2008).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

D. Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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  1. The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Michael S. Ewer

  2. The University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, 53792, WI, USA

    Steven M. Ewer

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Contributions

M. S. Ewer and S. M. Ewer contributed to discussion of content for the article, researched data to include in the manuscript, reviewed and edited the manuscript before submission, and revised the manuscript in response to the peer-reviewers' comments.

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Correspondence to Michael S. Ewer.

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Competing interests

M. S. Ewer has worked as a consultant for and received honoraria from Genentech/Roche. He has also received honoraria from Sanofi-Aventis. S. M. Ewer and the journal Chief Editor B. Mearns declare no competing interests.

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Ewer, M., Ewer, S. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat Rev Cardiol 7, 564–575 (2010). https://doi.org/10.1038/nrcardio.2010.121

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