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Lung cancer as a cardiotoxic state: a review

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Abstract

As the overall survival of patients with lung cancer continues to increase, more cancer survivors are faced with the risk of developing treatment-related cardiovascular toxicities. The increased knowledge of the molecular biology of non-small cell lung cancer has led to new and more personalized treatments. Nevertheless, the usual chemotherapy schemes and radiation therapy induce cardiac toxicities that are frequently underappreciated or go unnoticed. Up to date, the majority of cardiotoxicity studies have been focused in breast cancer, but new treatments in lung cancer patients, such as immune checkpoint-blocking antibodies or tyrosine kinase inhibitors, may also exert these cardiac toxic effects and therefore demand of the close collaboration of oncologists and cardiologists, in order to be addressed. The aim of this review is to provide more detailed information in regard to drug-induced cardiac toxicity focused in non-small cell lung cancer patients.

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References

  1. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur J Heart Fail. 2017;19(1):9–42.

    Article  PubMed  Google Scholar 

  2. Colzani E, Liljegren A, Johansson AL, et al. Prognosis of patients with breast cancer: causes of death and effects of time since diagnosis, age, and tumor characteristics. J Clin Oncol. 2011;29:4014–21.

    Article  PubMed  Google Scholar 

  3. Writing Group members, Mozaffarian D, Benjamin EJ, Go AS, American Heart Association Statistics Committee, Stroke Statistics Subcommittee, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133:e38–360.

    Article  Google Scholar 

  4. Pérez-Callejo D, Romero A, Provencio M, et al. Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring. Transl Lung Cancer Res. 2016;5(5):455–65.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wang K, Eblan MJ, Deal AM, et al. Cardiac toxicity after radiotherapy for stage III non-small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy. J Clin Oncol. 2017;35:1387.

    Article  PubMed  Google Scholar 

  6. Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments. Nat Rev Cardiol. 2015;12:547–58.

    Article  CAS  PubMed  Google Scholar 

  7. Fanous I, Dillon P. Cancer treatment-related cardiac toxicity: prevention, assessment and management. Med Oncol. 2016;33:1–11.

    Article  CAS  Google Scholar 

  8. Zagar TM, Cardinale DM, Marks LB. Breast cancer therapy-associated cardiovascular disease. Nat Rev Clin Oncol. 2016;13:172–84.

    Article  CAS  PubMed  Google Scholar 

  9. Heinzerling L, Ott PA, Hodi FS, et al. Cardiotoxicity associated with CTLA-4 and PD-1 blocking immunotherapy. J Immunother Cancer. 2016;16(4):50.

    Article  Google Scholar 

  10. Koene RJ, Prizment AE, Blaes A, et al. Shared risk factors in cardiovascular disease and cancer. Circulation. 2016;133:1104–14.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yu AF, Steingart RM, Fuster V. Cardiomyopathy associated with cancer therapy. J Card Fail. 2014;20(11):841–52.

    Article  PubMed  Google Scholar 

  12. Khakoo AY, Yeh ET. Therapy insight: management of cardiovascular disease in patients with cancer and cardiac complications of cancer therapy. Nat Clin Pract Oncol. 2008;5:655–67.

    Article  CAS  PubMed  Google Scholar 

  13. Lenihan DJ, Cardinale DM. Late cardiac effects of cancer treatment. J Clin Oncol. 2012;30:3657–64.

    Article  PubMed  Google Scholar 

  14. Hsiao S-H, Lin S-E, Chou Y-T, et al. Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer. Mol Clin Oncol. 2014;2(2):252–8.

    Article  PubMed  Google Scholar 

  15. Ruano-Ravina A, Torres-Durán M, Kelsey KT, Parente-Lamelas I, Leiro-Fernández V, Abdulkader I, et al. Residential radon, EGFR mutations and ALK alterations in never-smoking lung cancer cases. Eur Respir J. 2016;48(5):1462–70.

    Article  PubMed  Google Scholar 

  16. Kushi LH, Doyle C, McCullough M, et al. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2012;62:30–67.

    Article  PubMed  Google Scholar 

  17. Goff DC Jr, Brass L, Braun LT, American Heart Association Council on Epidemiology and Prevention, American Heart Association Council on Stroke, American Heart Association Council on Cardiovascular Nursing, American Heart Association Working Group on Quality of Care and Outcomes Research, American Heart Association Working Group on Atherosclerotic Peripheral Vascular Disease, et al. Essential features of a surveillance system to support the prevention and management of heart disease and stroke: a scientific statement from the American Heart Association Councils on epidemiology and prevention, stroke, and cardiovascular nursing and the interdisciplinary working groups on quality of care and outcomes research and atherosclerotic peripheral vascular disease. Circulation. 2007;115(1):127–55.

    Article  PubMed  Google Scholar 

  18. Lipshultz SE, Adams MJ, Colan SD, American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Basic Cardiovascular Sciences, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Radiology and Intervention, Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Nutrition Physical Activity and Metabolism, et al. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation. 2013;128:1927–95.

    Article  PubMed  Google Scholar 

  19. Schuchter LM, Hensley ML, Meropol NJ, Winer EP, American Society of Clinical Oncology Chemotherapy and Radiotherapy Expert Panel. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2002;20:2895–903.

    Article  PubMed  Google Scholar 

  20. Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS, et al. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol. 2007;25:3991–4008.

    Article  CAS  PubMed  Google Scholar 

  21. Jain D, Russell RR, Schwartz RG, et al. Cardiac complications of cancer therapy: pathophysiology, identification, prevention, treatment, and future directions. Curr Cardiol Rep. 2017;19(5):36.

    Article  PubMed  Google Scholar 

  22. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349:427–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Patel TV, Morgan JA, Demetri GD, et al. A preeclampsia-like syndrome characterized by reversible hypertension and proteinuria induced by the multitargeted kinase inhibitors sunitinib and sorafenib. J Natl Cancer Inst. 2008;100:282–4.

    Article  CAS  PubMed  Google Scholar 

  24. Jaworski C, Mariani JA, Wheeler G, et al. Cardiac complications of thoracic irradiation. J Am Coll Cardiol. 2013;61:2319–28.

    Article  PubMed  Google Scholar 

  25. Larsen RL, Jakacki RI, Vetter VL, et al. Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol. 1992;70:73–7.

    Article  CAS  PubMed  Google Scholar 

  26. Suter TM, Ewer MS. Cancer drugs and the heart: importance and management. Eur Heart J. 2013;34:1102–11.

    Article  CAS  PubMed  Google Scholar 

  27. Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375:1749–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Herrmann J, Lerman A, Sandhu NP, et al. Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Clin Proc. 2014;89:1287–306.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Strumberg D, Brugge S, Korn MW, et al. Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer. Ann Oncol. 2002;13:229–36.

    Article  CAS  PubMed  Google Scholar 

  30. Meinardi MT, Gietema JA, Van der Graaf WT, et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000;18:1725–32.

    Article  CAS  PubMed  Google Scholar 

  31. Provencio M, Bonilla F, Lacasta A, España P. Cerebral infarction after cisplatin-based chemotherapy. Postgrad Med J. 1994;70(825):525–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ma H, Jones KR, Guo R, et al. Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: role of endoplasmic reticulum stress. Clin Exp Pharmacol Physiol. 2010;37:460–5.

    Article  CAS  PubMed  Google Scholar 

  33. Rosa GM, Gigli L, Tagliasacchi MI, et al. Update on cardiotoxicity of anti-cancer treatments. Eur J Clin Invest. 2016;46(3):264–84.

    Article  PubMed  Google Scholar 

  34. Arbuck SG, Strauss H, Rowinsky E, et al. A reassessment of cardiac toxicity associated with taxol. J Natl Cancer Inst Monogr. 1993;15:117–30.

    Google Scholar 

  35. Rowinsky EK, McGuire WP, Guarnieri T, et al. Cardiac disturbances during the administration of taxol. J Clin Oncol. 1991;9:1704.

    Article  CAS  PubMed  Google Scholar 

  36. Fossella FV, Lee JS, Murphy WK, et al. Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer. J Clin Oncol. 1994;12(6):1238–44.

    Article  CAS  PubMed  Google Scholar 

  37. Oprea AD, Russell RR, Russell KS, et al. Chemotherapy agents with known cardiovascular side effects and their anesthetic implications. J Cardiothorac Vasc Anesth. 2015. doi:10.1053/j.jvca.2015.06.020.

    Google Scholar 

  38. Subar M, Muggia FM. Apparent myocardial ischemia associated with vinblastine administration. Cancer Treat Rep. 1986;70:690.

    CAS  PubMed  Google Scholar 

  39. Kantor AF, Greene MH, Boice JD, et al. Are vinca alkaloids associated with myocardial infarction? Lancet. 1981;1:1111.

    Article  CAS  PubMed  Google Scholar 

  40. Zabernigg A, Gattringer C. Myocardial infarction associated with vinorelbine (Navelbine). Eur J Cancer. 1996;32A:1618.

    Article  CAS  PubMed  Google Scholar 

  41. Cargill RI, Boyter AC, Lipworth BJ. Reversible myocardial ischaemia following vincristine containing chemotherapy. Respir Med. 1994;88:709.

    Article  CAS  PubMed  Google Scholar 

  42. Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov. 2016;15:385–403.

    Article  CAS  PubMed  Google Scholar 

  43. Li W, Croce K, Steensma DP, et al. Vascular and metabolic implications of novel targeted cancer therapies: focus on kinase inhibitors. J Am Coll Cardiol. 2015;66:1160–78.

    Article  PubMed  Google Scholar 

  44. Bair SM, Choueiri TK, Moslehi J. Cardiovascular complications associated with novel angiogenesis inhibitors: emerging evidence and evolving perspectives. Trends Cardiovasc Med. 2013;23:104–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  46. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542–50.

    Article  CAS  PubMed  Google Scholar 

  47. Chen J, Lu Y, Zheng Y. Incidence and risk of hypertension with bevacizumab in non-small-cell lung cancer patients: a meta-analysis of randomized controlled trials. Drug Des Develop Ther. 2015;18(9):4751–60.

    Google Scholar 

  48. An MM, Zou Z, Shen H, et al. Incidence and risk of significantly raised blood pressure in cancer patients treated with bevacizumab: an updated meta-analysis. Eur J Clin Pharmacol. 2010;66(8):813–21.

    Article  CAS  PubMed  Google Scholar 

  49. Nazer B, Humphreys B, Moslehi J. Effects of novel angiogenesis inhibitors for the treatment of cancer on the cardiovascular system. Focus on hypertension. Circulation. 2011;124:1687–91.

    Article  PubMed  Google Scholar 

  50. Maitland M, Bakris G, Black H, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitor. J Natl Cancer Inst. 2010;102(9):596–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Rees M, Khakoo A. Molecular mechanisms of hypertension and HF due to antiangiogenic cancer therapies. HF Clin. 2011;7:299–311.

    Google Scholar 

  52. Lankhorst S, Saleh L, Danser AJ, et al. Etiology of angiogenesis inhibition-related hypertension. Curr Opin Pharmacol. 2015;21:7–13.

    Article  CAS  PubMed  Google Scholar 

  53. López-Fernández T, Martín García A, Santaballa Beltrán A, et al. Cardio-onco-hematology in clinical practice. Position paper and recommendations. Rev Esp Cardiol (Engl Ed). 2017;70:474.

    Article  Google Scholar 

  54. Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. 2007;99:1232–9.

    Article  PubMed  Google Scholar 

  55. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665–73.

    Article  CAS  PubMed  Google Scholar 

  56. Reck M, Kaiser R, Mellemgaard A, et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014;2:143–55.

    Article  CAS  Google Scholar 

  57. Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009;361(10):958–67.

    Article  CAS  PubMed  Google Scholar 

  58. Kimberly RD, Robert LW, Dominique RT, et al. Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib and nilotinib in cardiomyocytes. Toxicol Appl Pharmacol. 2013;272:245–55.

    Article  CAS  Google Scholar 

  59. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–42.

    Article  CAS  PubMed  Google Scholar 

  60. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.

    Article  CAS  PubMed  Google Scholar 

  61. Wu YL, Zhou C, Liam CK, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015;26(9):1883–9.

    Article  PubMed  Google Scholar 

  62. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.

    Article  CAS  PubMed  Google Scholar 

  63. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011;29(21):2866–74.

    Article  CAS  PubMed  Google Scholar 

  64. Korashy HM, Attafi IM, Ansari MA, et al. Molecular mechanisms of cardiotoxicity of gefitinib in vivo and in vitro rat cardiomyocyte: role of apoptosis and oxidative stress. Toxicol Lett. 2016;11(252):50–61.

    Article  CAS  Google Scholar 

  65. Kanazawa S, Yamaguchi K, Kinoshita Y, et al. Gefitinib affects functions of platelets and blood vessels via changes in prostanoids balance. Clin Appl Thromb Hemost. 2005;11(4):429–34.

    Article  CAS  PubMed  Google Scholar 

  66. Shi Y, Zhang L, Liu X, et al. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013;14(10):953–61.

    Article  CAS  PubMed  Google Scholar 

  67. Biaoxue R, Hua L, Wenlong G, Shuanying Y. Efficacy and safety of icotinib in treating non-small cell lung cancer: a systematic evaluation and meta-analysis based on 15 studies. Oncotarget. 2016;7(52):86902–13.

    PubMed  PubMed Central  Google Scholar 

  68. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327–34.

    Article  CAS  PubMed  Google Scholar 

  69. Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:213.

    Article  CAS  PubMed  Google Scholar 

  70. Chen MH, Kerkelä R, Force T. Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation. 2008;118(1):84–95.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Michael SW, Kalpesh P, Dennis OB, et al. Cardiac safety of afatinib: a review of data from clinical trials. Cardio-Oncol. 2015;1:3.

    Article  Google Scholar 

  72. Thatcher N, Hirsch FR, Luft AV, et al. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015;16(7):763–74.

    Article  CAS  PubMed  Google Scholar 

  73. Smith DC, Powderly J, Lee JJ, et al. Evaluation of the effect of necitumumab on the corrected QT interval in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016;78(2):271–80.

    Article  CAS  PubMed  Google Scholar 

  74. Jänne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR Inhibitor-Resistant Non–Small-Cell Lung Cancer. N Engl J Med. 2015;372(18):1689–99.

    Article  PubMed  Google Scholar 

  75. European Medicines Agency – Tagrisso: Summary of the risk management plan (RMP) for Tagrisso (osimertinib). EMA/2497/2016. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004124/WC500202022.pdf Accessed on March 10, 2017.

  76. Soda M, Choi YL, Enamoto M, et al. Identification of the transforming EMLa-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561–6.

    Article  CAS  PubMed  Google Scholar 

  77. Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007;131(6):1190–203.

    Article  CAS  PubMed  Google Scholar 

  78. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small cell lung cancer. N Engl J Med. 2010;363(18):1693–703. doi:10.1056/NEJMoa1006448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Tartarone A, Gallucci G, Lazzari C, et al. Crizotinib-induced cardiotoxicity: the importance of a proactive monitoring and management. Future Oncol. 2015;11(14):2043–8.

    Article  CAS  PubMed  Google Scholar 

  80. Shaw AT, Kim DW, Nagakawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–94. doi:10.1056/NEJMoa1214886.

    Article  CAS  PubMed  Google Scholar 

  81. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–77. doi:10.1056/NEJMoa1408440.

    Article  PubMed  CAS  Google Scholar 

  82. Ou SH, Tong WP, Azada M, et al. Heart rate decrease during crizotinib treatment and potential correlation to clinical response. Cancer. 2013;119(11):1969–75. doi:10.1002/cncr.28040.

    Article  CAS  PubMed  Google Scholar 

  83. Weickhardt AJ, Rothman MS, Salian-Mehta S, et al. Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer. 2012;118(21):5302–9.

    Article  CAS  PubMed  Google Scholar 

  84. Zhang Z, Huang T-Q, Nepliouev I, et al. Crizotinib Inhibits Hyperpolarization-activated cyclic nucleotide-gated channel 4 activity. Cardiooncology. 2017;3:1.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. European Medicines Agency. Xalkori: Summary of the risk management plan (RMP) for Xalkori(Crizotinib). EMA/CHMP/465053/2015 http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002489/WC500134759.pdf Accessed on March 10, 2017.

  86. Wu J, Savooji J, Liu D. Second- and third-generation ALK inhibitors for non-small cell lung cancer. J Hematol Oncol. 2016;8(9):19. doi:10.1186/s13045-016-0251-8.

    Article  CAS  Google Scholar 

  87. European Medicines Agency. Zykadia: Summary of the risk management plan (RMP) for Zykadia (Ceritinib). EMA/170114/2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003819/WC500187504.pdf Accessed on March 10, 2017.

  88. Shaw AT, Gandhi L, Gadgeel S, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016;17(2):234–42. doi:10.1016/S1470-2045(15)00488-X.

    Article  CAS  PubMed  Google Scholar 

  89. Ou SHI, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. 2016;34(7):661–8. doi:10.1200/JCO.2015.63.9443.

    Article  CAS  PubMed  Google Scholar 

  90. Morcos PN, Bogman K, Hubeaux S, et al. Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies. Cancer Chemother Pharmacol. 2017;. doi:10.1007/s00280-017-3253-5.

    PubMed  Google Scholar 

  91. Gettinger SN, Bazhenova LA, Langer CJ, et al. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial. Lancet Oncol. 2016;17(12):1683–96.

    Article  CAS  PubMed  Google Scholar 

  92. Abdel-Rahman O, Helbling D, Schmidt J, et al. Treatment-related death in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Clin Oncol (R Coll Radiol). 2017;29(4):218–30.

    Article  CAS  Google Scholar 

  93. Pardoll D. The blockade of immune checkpoints in cancer immunotherapy. Nav Rev Cancer. 2012;12(4):252–64.

    Article  CAS  Google Scholar 

  94. Tarrio ML, Grabie N, Bu DX, et al. PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis. J Immunol. 2012;188(10):4876–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291(5502):319–22.

    Article  CAS  PubMed  Google Scholar 

  96. Okazaki T, Tanaka Y, Nishio R, et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003;9(12):1477–83.

    Article  CAS  PubMed  Google Scholar 

  97. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-cell lung cancer. N Engl J Med. 2015;373(2):123–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.

    Article  CAS  PubMed  Google Scholar 

  99. Agrawal S, Waxman I, Lambert A, et al. Evaluation of the potential for QTc prolongation in patients with solid tumors receiving nivolumab. Cancer Chemother Pharmacol. 2016;77(3):635–41.

    Article  CAS  PubMed  Google Scholar 

  100. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33.

    Article  CAS  PubMed  Google Scholar 

  101. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.

    Article  PubMed  Google Scholar 

  102. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.

    Article  CAS  PubMed  Google Scholar 

  103. Läubli H, Balmelli C, Bossard M, et al. Acute HF due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma. J Immunother Cancer. 2015;21(3):11.

    Article  Google Scholar 

  104. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicenter randomised controlled trial. Lancet. 2017;389(10066):255–65.

    Article  PubMed  Google Scholar 

  105. Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387(10030):1837–46.

    Article  CAS  PubMed  Google Scholar 

  106. Voskens CJ, Goldinger SM, Loquai C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS ONE. 2013;8(1):e53745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Yun S, Vincelette ND, Mansour I, et al. Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication. Case Rep Oncol Med. 2015;2015:794842.

    PubMed  PubMed Central  Google Scholar 

  108. Geisler BP, Raad RA, Esaian D, et al. Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome. J Immunother Cancer. 2015;17(3):4.

    Article  Google Scholar 

  109. Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16(5):522–30.

    Article  CAS  PubMed  Google Scholar 

  110. Cubbon RM, Lyon AR. Cardio-oncology: concepts and practice. Indian Heart J. 2016;68(1):S77–85.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Omersa D, Cufer T, Marcun R, et al. Echocardiography and cardiac biomarkers in patients with non-small cell lung cancer treated with platinum-based chemotherapy. Radiol Oncol. 2017;51(1):15–22.

    Article  PubMed  Google Scholar 

  112. Thavendiranathan P, Poulin F, Lim KD, et al. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol. 2014;63((25 Pt A)):2751–68.

    Article  PubMed  Google Scholar 

  113. Ming X, Feng Y, Yang C, et al. Radiation-induced heart disease in lung cancer radiotherapy: a dosimetric update. Med (Baltimore). 2016;95(41):e5051.

    Article  CAS  Google Scholar 

  114. Patil H, Vaidya O, Bogart D. A review of causes and systemic approach to cardiac troponin elevation. Clin Cardiol. 2011;34(12):723–8.

    Article  PubMed  Google Scholar 

  115. Cardinale D, Sandri MT, Colombo A, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Rivista Italiana della Medicina di Laboratorio. 2005;1(1):38–43.

    Google Scholar 

  116. Lainscak M, von Haehling S, Anker SD. Natriuretic peptides and other biomarkers in chronic heart failure: from BNP, NT-proBNP, and MR-proANP to routine biochemical markers. Int J Cardiol. 2009;132(3):303–11.

    Article  PubMed  Google Scholar 

  117. Berardi R, Caramanti M, Savini A, et al. State of the art for cardiotoxicity due to chemotherapy and to targeted therapies: a literature review. Crit Rev Oncol Hematol. 2013;88(1):75–86.

    Article  PubMed  Google Scholar 

  118. Brana I, Tabernero J. Cardiotoxicity. Ann Oncol. 2010;21(Suppl 7):vii173–9.

    PubMed  Google Scholar 

  119. Cardinale D, Biasillo G, Cipolla CM. Curing cancer, saving the heart: a challenge that cardioncology should not miss. Curr Cardiol Rep. 2016;18(6):51.

    Article  PubMed  Google Scholar 

  120. Curigliano G, Cardinale D, Dent S, et al. Cardiotoxicity of anticancer treatments: epidemiology, detection, and management. CA Cancer J Clin. 2016;66(4):309–25.

    Article  PubMed  Google Scholar 

  121. Mishra SI, Scherer RW, Snyder C, et al. Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev. 2012;8:CD008465.

    Google Scholar 

  122. Wiskemann J, Hummler S, Diepold C, et al. POSITIVE study: physical exercise program in non-operable lung cancer patients undergoing palliative treatment. BMC Cancer. 2016;19(16):499.

    Article  Google Scholar 

  123. Michaels C. The importance of exercise in lung cancer treatment. Transl Lung Cancer Res. 2016;5(3):235–8.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Kuehr L, Wiskemann J, Abel U, et al. Exercise in patients with non-small cell lung cancer. Med Sci Sports Exerc. 2014;46(4):656–63.

    Article  PubMed  Google Scholar 

  125. Shiels MS, Gibson T, Sampson J, et al. Cigarette smoking prior to first cancer and risk of second smoking-associated cancers among survivors of bladder, kidney, head and neck, and stage I lung cancers. J Clin Oncol. 2014;32(35):3989–95.

    Article  PubMed  PubMed Central  Google Scholar 

  126. McCarter K, Martínez Ú, Britton B, et al. Smoking cessation care among patients with head and neck cancer: a systematic review. BMJ Open. 2016;6(9):e012296.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Latino-Martel P, Arwidson P, Ancellin R, et al. Alcohol consumption and cancer risk: revisiting guidelines for sensible drinking. CMAJ. 2011;183(16):1861–5.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Cardinale D, Biasillo G, Salvatici M, et al. Using biomarkers to predict and to prevent cardiotoxicity of cancer therapy. Expert Rev Mol Diagn. 2017;17(3):245–56.

    Article  CAS  PubMed  Google Scholar 

  129. Cardinale D, Bacchiani G, Beggiato M, et al. Strategies to prevent and treat cardiovascular risk in cancer patients. Semin Oncol. 2013;40(2):186–98.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology Department, Hospital Universitario Puerta de Hierro Majadahonda, C/Manuel de Falla 1, 28222, Majadahonda, Madrid, Spain

    David Pérez-Callejo, María Torrente, María Auxiliadora Brenes, Beatriz Núñez & Mariano Provencio

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  1. David Pérez-Callejo
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  2. María Torrente
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  3. María Auxiliadora Brenes
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  4. Beatriz Núñez
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  5. Mariano Provencio
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David Pérez-Callejo and María Torrente have contributed equally to this work.

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Correspondence to María Torrente.

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Pérez-Callejo, D., Torrente, M., Brenes, M.A. et al. Lung cancer as a cardiotoxic state: a review. Med Oncol 34, 159 (2017). https://doi.org/10.1007/s12032-017-1012-4

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