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Victims of Our Own Success: Cardiac Toxicities from Conventional and Emerging Cancer Therapies

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The MASCC Textbook of Cancer Supportive Care and Survivorship

Abstract

Recent advances in diagnostic and treatment strategies for various cancers suggest that the number of cancer survivors will continue to grow over the next few decades. Coupled with the aggressiveness of new chemotherapy regimens, emergence of molecularly targeted agents, frequent use of dual modality treatments that combine systemic therapy with radiation, the incidence of treatment-related side effects will also likely continue to increase. Due, in part, to its diverse clinical manifestations and significant morbidity burden, prompt diagnosis and effective management of cardiotoxicity can be particularly challenging for members of the cancer care team. In order to optimize care and follow-up for the growing population of cancer patients and survivors, a basic understanding of the risk factors, treatments, and outcomes for the various cardiac toxicities is absolutely essential. Herein, the cardiotoxicity profiles of several relevant classes of anticancer agents are discussed, with emphasis on anthracyclines, trastuzumab, molecularly targeted agents, and radiotherapy. A brief outline of the causes and underlying pathophysiology as well as management and prognosis of the different cardiac manifestations is introduced and explored.

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References

  1. Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342(15):1077–84.

    Article  CAS  PubMed  Google Scholar 

  2. Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131(22):1981–8.

    Article  CAS  PubMed  Google Scholar 

  3. Groarke JD, Nohria A. Anthracycline cardiotoxicity: a new paradigm for an old classic. Circulation. 2015;131(22):1946–9.

    Article  PubMed  Google Scholar 

  4. Volkova M, Russell R 3rd. Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev. 2011;7(4):214–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Elliott P. Pathogenesis of cardiotoxicity induced by anthracyclines. Semin Oncol. 2006;33(3 Suppl 8):S2–7.

    Article  CAS  PubMed  Google Scholar 

  6. Lyu YL, Kerrigan JE, Lin CP, et al. Topoisomerase II beta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res. 2007;67(18):8839–46.

    Article  CAS  PubMed  Google Scholar 

  7. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869–79.

    Article  CAS  PubMed  Google Scholar 

  8. Hershman DL, McBride RB, Eisenberger A, et al. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2008;26(19):3159–65.

    Article  CAS  PubMed  Google Scholar 

  9. Shapiro CL, Hardenbergh PH, Gelman R, et al. Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J Clin Oncol. 1998;16(11):3493–501.

    Article  CAS  PubMed  Google Scholar 

  10. Bria E, Giannarelli D, Felici A, et al. Taxanes with anthracyclines as first-line chemotherapy for metastatic breast carcinoma. Cancer. 2005;103(4):672–9.

    Article  CAS  PubMed  Google Scholar 

  11. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.

    Article  CAS  PubMed  Google Scholar 

  12. Wang X, Liu W, Sun CL, et al. Hyaluronan synthase 3 variant and anthracycline-related cardiomyopathy: a report from the children's oncology group. J Clin Oncol. 2014;32(7):647–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nakamae H, Tsumura K, Terada Y, et al. Notable effects of angiotensin II receptor blocker, valsartan, on acute cardiotoxic changes after standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Cancer. 2005;104(11):2492–8.

    Article  CAS  PubMed  Google Scholar 

  14. van Dalen EC, van der Pal HJ, Caron HN, et al. Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy. Cochrane Database Syst Rev. 2006;4:CD005008.

    Google Scholar 

  15. Gabizon AA, Lyass O, Berry GJ, et al. Cardiac safety of pegylated liposomal doxorubicin (Doxil/Caelyx) demonstrated by endomyocardial biopsy in patients with advanced malignancies. Cancer Investig. 2004;22(5):663–9.

    Article  CAS  Google Scholar 

  16. Seifert CF, Nesser ME, Thompson DF. Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity. Ann Pharmacother. 1994;28(9):1063–72.

    Article  CAS  PubMed  Google Scholar 

  17. Smith LA, Cornelius VR, Plummer CJ, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 2010;10:337.

    Article  PubMed  PubMed Central  Google Scholar 

  18. van Dalen EC, Caron HN, Dickinson HO, et al. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev. 2005;1:CD003917.

    Google Scholar 

  19. Swain SM, Whaley FS, Gerber MC, et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol. 1997;15(4):1318–32.

    Article  CAS  PubMed  Google Scholar 

  20. Gulati G, Heck SL, Ree AH, 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(21):1671–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bosch X, Rovira M, Sitges M, 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(23):2355–62.

    Article  CAS  PubMed  Google Scholar 

  22. Kalay N, Basar E, Ozdogru I, et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006;48(11):2258–62.

    Article  CAS  PubMed  Google Scholar 

  23. Jiji RS, Kramer CM, Salerno M. Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs. J Nucl Cardiol. 2012;19(2):377–88.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kuittinen T, Husso-Saastamoinen M, Sipola P, et al. Very acute cardiac toxicity during BEAC chemotherapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transplant. 2005;36(12):1077–82.

    Article  CAS  PubMed  Google Scholar 

  25. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation. 2007;116(19):2216–33.

    Article  PubMed  Google Scholar 

  26. Jensen BV, Skovsgaard T, Nielsen SL. Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol. 2002;13(5):699–709.

    Article  CAS  PubMed  Google Scholar 

  27. Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005;23(31):7820–6.

    Article  CAS  PubMed  Google Scholar 

  28. Crone SA, Zhao YY, Fan L, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002;8(5):459–65.

    Article  CAS  PubMed  Google Scholar 

  29. Perik PJ, de Vries EG, Gietema JA, et al. Serum HER2 levels are increased in patients with chronic heart failure. Eur J Heart Fail. 2007;9(2):173–7.

    Article  CAS  PubMed  Google Scholar 

  30. Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20(5):1215–21.

    Article  CAS  PubMed  Google Scholar 

  31. Ewer MS, Lippman SM. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. J Clin Oncol. 2005;23(13):2900–2.

    Article  CAS  PubMed  Google Scholar 

  32. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354(8):809–20.

    Article  CAS  PubMed  Google Scholar 

  33. Pivot X, Romieu G, Debled M, et al. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013;14(8):741–8.

    Article  CAS  PubMed  Google Scholar 

  34. Robert NJ, Eiermann W, Pienkowski T, et al. BCIRG 006: Docetaxel and trastuzumab-based regimens improve DFS and OS over AC-T in node positive and high risk node negative HER2 positive early breast cancer patients: quality of life (QOL) at 36 months follow-up. J Clin Oncol. 2007;25(90180):19647.

    Google Scholar 

  35. Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2014;27(9):911–39.

    Article  PubMed  Google Scholar 

  36. Tan-Chiu E, Yothers G, Romond 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. 2005;23(31):7811–9.

    Article  CAS  PubMed  Google Scholar 

  37. Mackey JR, Clemons M, Cote MA, et al. Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab working group. Curr Oncol. 2008;15(1):24–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol. 2006;24(25):4107–15.

    Article  CAS  PubMed  Google Scholar 

  39. Perez EA, Koehler M, Byrne J, et al. Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin Proc. 2008;83(6):679–86.

    Article  PubMed  Google Scholar 

  40. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Aleman BM, van den Belt-Dusebout AW, De Bruin ML, et al. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. 2007;109(5):1878–86.

    Article  CAS  PubMed  Google Scholar 

  42. Hardenbergh PH, Munley MT, Bentel GC, et al. Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin: preliminary results. Int J Radiat Oncol Biol Phys. 2001;49(4):1023–8.

    Article  CAS  PubMed  Google Scholar 

  43. Hooning MJ, Botma A, Aleman BM, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99(5):365–75.

    Article  PubMed  Google Scholar 

  44. Akhtar SS, Salim KP, Bano ZA. Symptomatic cardiotoxicity with high-dose 5-fluorouracil infusion: a prospective study. Oncology. 1993;50(6):441–4.

    Article  CAS  PubMed  Google Scholar 

  45. Ng M, Cunningham D, Norman AR. The frequency and pattern of cardiotoxicity observed with capecitabine used in conjunction with oxaliplatin in patients treated for advanced colorectal cancer (CRC). Eur J Cancer. 2005;41(11):1542–6.

    Article  CAS  PubMed  Google Scholar 

  46. Malhotra V, Dorr VJ, Lyss AP, et al. Neoadjuvant and adjuvant chemotherapy with doxorubicin and docetaxel in locally advanced breast cancer. Clin Breast Cancer. 2004;5(5):377–84.

    Article  CAS  PubMed  Google Scholar 

  47. Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med. 2016;375(15):1457–67.

    Article  CAS  PubMed  Google Scholar 

  48. Dahlberg SE, Sandler AB, Brahmer JR, et al. Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599. J Clin Oncol. 2010;28(6):949–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Khakoo AY, Kassiotis CM, Tannir N, et al. Heart failure associated with sunitinib malate: a multitargeted receptor tyrosine kinase inhibitor. Cancer. 2008;112(11):2500–8.

    Article  CAS  PubMed  Google Scholar 

  50. Zang J, Wu S, Tang L, et al. Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: a systematic review and meta-analysis. PLoS One. 2012;7(2):e30353.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bellinger AM, Arteaga CL, Force T, et al. Cardio-oncology: how new targeted cancer therapies and precision medicine can inform cardiovascular discovery. Circulation. 2015;132(23):2248–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Winson Y. Cheung .

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Samawi, H.H., Cheung, W.Y. (2018). Victims of Our Own Success: Cardiac Toxicities from Conventional and Emerging Cancer Therapies. In: Olver, I. (eds) The MASCC Textbook of Cancer Supportive Care and Survivorship. Springer, Cham. https://doi.org/10.1007/978-3-319-90990-5_11

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  • DOI: https://doi.org/10.1007/978-3-319-90990-5_11

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