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Mechanisms of Cardiovascular Damage Induced by Traditional Chemotherapy

  • Valentina Mercurio
  • Giulio Agnetti
  • Pasquale Pagliaro
  • Carlo G. Tocchetti
Chapter
Part of the Current Clinical Pathology book series (CCPATH)

Abstract

Traditional chemotherapeutics are essential tools in the management of cancer patients. Nevertheless, these drugs are burdened by some degree of cardiovascular toxicity. Anthracycline-induced toxicity has been historically the most studied, but also the use of other drugs can be limited by a certain risk of cardiac and vascular toxicities. Here we acknowledge the main mechanistic insights, and we describe the different aspects of cardiotoxicity of these drugs, highlighting the different cellular compartments and cardiovascular components affected.

Keywords

Chemotherapy Cardiovascular toxicity Cardiomyocytes Endothelial cells Oxidative stress 

Notes

Disclosures

CGT received speaking fees from Alere.

Funding

CGT is funded by a Federico II University/Ricerca di Ateneo grant.

References

  1. 1.
    Brutsaert DL. Cardiac endothelial–myocardial signaling: its role in cardiac growth, contractile performance, and rhythmicity. Physiol Rev. 2003;83:59–115.CrossRefGoogle Scholar
  2. 2.
    Tirziu D, Giordano FJ, Simons M. Cell communications in the heart. Circulation. 2010;122:928–6.CrossRefGoogle Scholar
  3. 3.
    Zhao Y, Sawyer DR, Baliga RR, Opel DJ, Han X, Marchionni MA. Neuregulins promote survival and growth of cardiac myocytes. J Biol Chem. 1998;273:10261–9.CrossRefGoogle Scholar
  4. 4.
    Park K-A, Park WJ. Endothelial dysfunction: clinical complications in cardiovascular disease and therapeutic approaches. J Korean Med Sci. 2015;30:1213–25.CrossRefGoogle Scholar
  5. 5.
    Morganti M, Carpi A, Nicolini A, Gorini I, Glaviano B, Fini M, et al. Atherosclerosis and cancer: common pathways on the vascular endothelium. Biomed Pharmacother. 2002;56:317–24.CrossRefGoogle Scholar
  6. 6.
    Cardinale D, Bacchiani G, Beggiato M, Colombo A, Cipolla CM. Strategies to prevent and treat cardiovascular risk in cancer patients. Semin Oncol. 2013;40:186–98.CrossRefGoogle Scholar
  7. 7.
    Di Lisi D, Madonna R, Zito C, Bronte E, Badalamenti G, Parrella P, et al. Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond. Int J Cardiol. 2017;227:11–7.CrossRefGoogle Scholar
  8. 8.
    Soultati A, Mountzios G, Avgerinou C, Papaxoinis G, Pectasides D, Dimopoulos M-A, et al. Endothelial vascular toxicity from chemotherapeutic agents: preclinical evidence and clinical implications. Cancer Treat Rev. 2012;38:473–83.CrossRefGoogle Scholar
  9. 9.
    Tocchetti CG, Cadeddu C, Di Lisi D, Femminò S, Madonna R, Mele D, et al. From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: a translational overview. Antioxid Redox Signal. 2017;  https://doi.org/10.1089/ars.2016.6930. [Epub ahead of print]
  10. 10.
    Wolf MB, Baynes JW. The anti-cancer drug, doxorubicin, causes oxidant stress induced endothelial dysfunction. Biochim Biophys Acta. 2006;1760:267–71.CrossRefGoogle Scholar
  11. 11.
    Kalyanaraman B. Teaching the basics of redox biology to medical and graduate students: oxidants, antioxidants and disease mechanisms. Redox Biol. 2013;1:244–57.CrossRefGoogle Scholar
  12. 12.
    Wojcik T, Buczek E, Majzner K, Kolodziejczyk A, Miszczyk J, Kwiatek W, et al. Comparative endothelial profiling of doxorubicin and daunorubicin in cultured endothelial cells. Toxicol In Vitro. 2015;29(3):512–21.CrossRefGoogle Scholar
  13. 13.
    Krohn K. Topics in current chemistry. In: Anthracycline chemistry and biology: biological occurrence and biosynthesis, synthesis and chemistry. New York: Springer; 2008.Google Scholar
  14. 14.
    Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56(2):185–229.CrossRefGoogle Scholar
  15. 15.
    Majzner K, Wo’jcik T, Szafraniec E, Łukawska M, Oszczapowicz I, Chłopicki S, et al. Raman microspectroscopic investigation on nuclear accumulation of doxorubicin, daunorubicin and their epimers in endothelium; relationship with cytotoxicity. Analyst. 2015;140:2302–10.CrossRefGoogle Scholar
  16. 16.
    Volkova M, Russell R 3rd. Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev. 2011;7(4):214–20.CrossRefGoogle Scholar
  17. 17.
    Friedberg EC. Out of the shadows and into the light: the emergence of DNA repair. Trends Biochem Sci. 1995;20:381.CrossRefGoogle Scholar
  18. 18.
    Cortez D, Guntuku S, Qin J, Elledge SJ. ATR and ATRIP: partners in checkpoint signaling. Science. 2001;294:1713–6.CrossRefGoogle Scholar
  19. 19.
    Feng R, Zhai WL, Yang HY, Jin H, Zhang QX. Induction of ER stress protects gastric cancer cells against apoptosis induced by cisplatin and doxorubicin through activation of p38 MAPK. Biochem Biophys Res Commun. 2011;406:299–304.CrossRefGoogle Scholar
  20. 20.
    Diers AR, Broniowska KA, Hogg N. Nitrosative stress and redox-cycling agents synergize to cause mitochondrial dysfunction and cell death in endothelial cells. Redox Biol. 2013;1:1–7.CrossRefGoogle Scholar
  21. 21.
    Faneyte IF, Kristel PMP, Van De Vijver MJ. Multidrug resistance associated genes MRP1, MRP2 and MRP3 in primary and anthracycline exposed breast cancer. Anticancer Res. 2004;24:2931–40.PubMedGoogle Scholar
  22. 22.
    Bains OS, Szeitz A, Lubieniecka JM, Cragg GE, Grigliatti TA, Riggs KW, et al. A correlation between cytotoxicity and reductase-mediated metabolism in cell lines treated with doxorubicin and daunorubicin. J Pharmacol Exp Ther. 2013;347:375–87.CrossRefGoogle Scholar
  23. 23.
    Tewey K, Rowe T, Yang L, Halligan B, Liu L. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984;226:466–8.CrossRefGoogle Scholar
  24. 24.
    Wang JC. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol. 2002;3:430–40.CrossRefGoogle Scholar
  25. 25.
    Zhang S, Liu X, Bawa-Khalfe T, Lu L-S, Lyu YL, Liu LF, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18:1639–42.CrossRefGoogle Scholar
  26. 26.
    Capranico G, Tinelli S, Austin CA, Fisher ML, Zunino F. Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta. 1992;1132:43–8.CrossRefGoogle Scholar
  27. 27.
    Salvatorelli E, Menna P, Paz OG, Chello M, Covino E, Singer JW, et al. The novel anthracenedione, pixantrone, lacks redox activity and inhibits doxorubicinol formation in human myocardium: insight to explain the cardiac safety of pixantrone in doxorubicin-treated patients. J Pharmacol Exp Ther. 2013;344(2):467–78.CrossRefGoogle Scholar
  28. 28.
    Herbrecht R, Cernohous P, Engert A, Le Gouill S, Macdonald D, Machida C, et al. Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. Ann Oncol. 2013;24(10):2618–23.CrossRefGoogle Scholar
  29. 29.
    Toldo S, Goehe RW, Lotrionte M, Mezzaroma E, Sumner ET, Biondi-Zoccai GGL, et al. Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. PLoS One. 2013;8:4–11.CrossRefGoogle Scholar
  30. 30.
    Kaushal V, Kaushal GP, Mehta P. Differential toxicity of anthracyclines on cultured endothelial cells. Endothelium. 2004;11:253–8.CrossRefGoogle Scholar
  31. 31.
    Grover S, Lou PW, Bradbrook C, Cheong K, Kotasek D, Leong DP, et al. Early and late changes in markers of aortic stiffness with breast cancer therapy. Intern Med J. 2015;45:140–7.CrossRefGoogle Scholar
  32. 32.
    Krystal JI, Reppucci M, Mayr T, Fish JD, Sethna C. Arterial stiffness in childhood cancer survivors. Pediatr Blood Cancer. 2015;62:1832–7.CrossRefGoogle Scholar
  33. 33.
    Noordhuis P, Holwerda U, Van der Wilt CL, Van Groeningen CJ, Smid K, Meijer S, et al. 5-Fluorouracil incorporation into RNA and DNA in relation to thymidylate synthase inhibition of human colorectal cancers. Ann Oncol. 2004;15(7):1025–32.CrossRefGoogle Scholar
  34. 34.
    Kosmas C, Kallistratos MS, Kopterides P, Syrios J, Skopelitis H, Mylonakis N, et al. Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol. 2008;134(1):75–82. Epub 2007 Jul 17CrossRefGoogle Scholar
  35. 35.
    Lestuzzi C, Tartuferi L, Corona G. Capecitabine (and 5 fluorouracil) cardiotoxicity. Metabolic considerations. Breast J. 2011;17:564–5.CrossRefGoogle Scholar
  36. 36.
    Miura K, Kinouchi M, Ishida K, Kinouchi M, Ishida K, Fujibuchi W, et al. 5-FU metabolism in cancer and orally-administrable 5-FU drugs. Cancer (Basel). 2010;2:1717–30.CrossRefGoogle Scholar
  37. 37.
    Basaki Y, Chikahisa L, Aoyagi K, Miyadera K, Yonekura K, Hashimoto A, et al. Gamma-Hydroxybutyric acid and 5-fluorouracil, metabolites of UFT, inhibit the angiogenesis induced by vascular endothelial growth factor. Angiogenesis. 2001;4:163–73.CrossRefGoogle Scholar
  38. 38.
    Kinhult S, Albertsson M, Eskilsson J, Cwikiel M. Effects on probucol on endothelial damage by 5-fluorouracil. Acta Oncol. 2003;42:304–8.CrossRefGoogle Scholar
  39. 39.
    Kuenen BC, Levi M, Meijers JC, Kakkar AK, van Hinsbergh VW, Kostense PJ, et al. Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients. Arterioscler Thromb Vasc Biol. 2002;22:1500–5.CrossRefGoogle Scholar
  40. 40.
    Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol. 2009;48:9–17.CrossRefGoogle Scholar
  41. 41.
    Telli ML, Hunt SA, Carlson RW, Guardino AE. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol. 2007;25:3525–33.CrossRefGoogle Scholar
  42. 42.
    Cianci G, Morelli MF, Cannita K, Morese R, Ricevuto E, Di Rocco ZC, et al. Prophylactic options in patients with 5-fluorouracil associated cardiotoxicity. Br J Cancer. 2003;88:1507–9.CrossRefGoogle Scholar
  43. 43.
    Shoemaker LK, Arora U, Rocha Lima CM. 5-fluorouracil-induced coronary vasospasm. Cancer Control. 2004;11:46–9.CrossRefGoogle Scholar
  44. 44.
    Lamberti M, Porto S, Zappavigna S, Addeo E, Marra M, Miraglia N, Sannolo N, Vanacore D, Stiuso P, Caraglia M. A mechanistic study on the cardiotoxicity of 5-fluorouracil in vitro and clinical and occupational perspectives. Toxicol Lett. 2014;227(3):151–6.CrossRefGoogle Scholar
  45. 45.
    Mazarakis A, Goudevenos J, Kounis NG, et al. Coronary vasospasm induced by cytostatic drugs: Kounis syndrome seems to be the most likely culprit. Hell J Cardiol. 2013;54:482–5.Google Scholar
  46. 46.
    Fontanella C, Aita M, Cinausero M, Aprile G, Baldin MG, Dusi V, et al. Capecitabine induced cardiotoxicity: more evidence or clinical approaches to protect the patients’ heart? Onco Targets Ther. 2014;7:1783–91.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Jensen SA, Sørensen JB. Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine. Cancer Chemother Pharmacol. 2006;58:487–93.CrossRefGoogle Scholar
  48. 48.
    Jensen SA, Sørensen JB. 5-fluorouracil-based therapy induces endovascular injury having potential significanceto development of clinically overt cardiotoxicity. Cancer Chemother Pharmacol. 2012;69:57–64.CrossRefGoogle Scholar
  49. 49.
    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;41:1542–6.CrossRefGoogle Scholar
  50. 50.
    Tsibiribi P, Bui-Xuan C, Bui-Xuan B, Lombard-Bohas C, Duperret S, Belkhiria M, et al. Cardiac lesions induced by 5-fluorouracil in the rabbit. Hum Exp Toxicol. 2006;25:305–9.CrossRefGoogle Scholar
  51. 51.
    Herrmann J, Yang EH, Iliescu CA, Cilingiroglu M, Charitakis K, Hakeem A, et al. Vascular toxicities of cancer therapies: the old and the new – an evolving avenue. Circulation. 2016;133(13):1272–89.CrossRefGoogle Scholar
  52. 52.
    Lechner D, Kollars M, Gleiss A, Kyrle PA, Weltermann A. Chemotherapy induced thrombin generation via procoagulant endothelial microparticles is independent of tissue factor activity. J Thromb Haemost. 2007;5:2445–52.CrossRefGoogle Scholar
  53. 53.
    Ito H, Okafuji T, Suzuki T. Vitamin E prevents endothelial injury associated with cisplatin injection into the superior mesenteric artery of rats. Heart Vessel. 1995;10:178–84.CrossRefGoogle Scholar
  54. 54.
    Ferroni P, Della-Morte D, Palmirotta R, McClendon M, Testa G, Abete P, et al. Platinum-based compounds and risk for cardiovascular toxicity in the elderly: role of the antioxidants in chemoprevention. Rejuvenation Res. 2011;14(3):293–308.CrossRefGoogle Scholar
  55. 55.
    Nuver J, Smit AJ, Sleijfer DT, Van Gessel AI, Van Roon AM, Van Der Meer J, et al. Microalbuminuria, decreased fibrinolysis, and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer. Eur J Cancer. 2004;40:701–6.CrossRefGoogle Scholar
  56. 56.
    Vaughn DJ, Palmer SC, Carver JR, Jacobs LA, Mohler ER. Cardiovascular risk in long-term survivors of testicular cancer. Cancer. 2008;112:1949–53.CrossRefGoogle Scholar
  57. 57.
    Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826):1591–601.CrossRefGoogle Scholar
  58. 58.
    Hotchkiss KA, Ashton AW, Mahmood R, Russell RG, Sparano JA, Schwartz EL. Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel (Taxotere): association with impaired repositioning of the microtubule organizing center. Mol Cancer Ther. 2002;1:1191–200.PubMedGoogle Scholar
  59. 59.
    Wood SC, Tang X, Tesfamariam B. Paclitaxel potentiates inflammatory cytokine induced prothrombotic molecules in endothelial cells. J Cardiovasc Pharmacol. 2010;55:276–85.CrossRefGoogle Scholar
  60. 60.
    Mikaelian I, Buness A, de Vera-Mudry MC, Kanwal C, Coluccio D, Rasmussen E, et al. Primary endothelial damage is the mechanism of cardiotoxicity of tubulin-binding drugs. Toxicol Sci. 2010;117:144–51.CrossRefGoogle Scholar
  61. 61.
    Kachel DL, Martin WJ. Cyclophosphamide-induced lung toxicity: mechanism of endothelial cell injury. J Pharmacol Exp Ther. 1994;268:42–6.PubMedGoogle Scholar
  62. 62.
    Samuels BL, Vogelzang NJ, Kennedy BJ. Severe vascular toxicity associated with vinblastine, bleomycin, and cisplatin chemotherapy. Cancer Chemother Pharmacol. 1987;19:253–6.CrossRefGoogle Scholar
  63. 63.
    Hansen ES. International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/2. Shared risk factors for cancer and atherosclerosis – a review of the epidemiological evidence. Mutat Res. 1990;239:163–79.CrossRefGoogle Scholar
  64. 64.
    Haugnes HS, Wethal T, Aass N, Dahl O, Klepp O, Langberg CW, et al. Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study. J Clin Oncol. 2010;28:4649–57.CrossRefGoogle Scholar
  65. 65.
    Meinardi MT, Gietema JA, van der Graaf WT, van Veldhuisen DJ, Runne MA, Sluiter WJ, et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000;18:1725–32.CrossRefGoogle Scholar
  66. 66.
    Arima Y, Oshima S, Noda K, Fukushima H, Taniguchi I, Nakamura S, et al. Sorafenib-induced acute myocardial infarction due to coronary artery spasm. J Cardiol. 2009;54:512–5.  https://doi.org/10.1016/j.jjcc.2009.03.009.CrossRefPubMedGoogle Scholar
  67. 67.
    Gemici G, Cinçin A, Değertekin M, Oktay A. Paclitaxel-induced ST-segment elevations. Clin Cardiol. 2009;32:E94–6.  https://doi.org/10.1002/clc.20291.CrossRefPubMedGoogle Scholar
  68. 68.
    Shah K, Gupta S, Ghosh J, Bajpai J, Maheshwari A. Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: a case report and review of literature. J Cancer Res Ther. 2012;8:442–4.CrossRefGoogle Scholar
  69. 69.
    Petrelli F, Cabiddu M, Borgonovo K, Barni S. Risk of venous and arterial thromboembolic events associated with anti-EGFR agents: a meta-analysis of randomized clinical trials. Ann Oncol. 2012;23:1672–9.CrossRefGoogle Scholar
  70. 70.
    Choueiri TK, Schutz FA, Je Y, Rosenberg JE, Bellmunt J. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. J Clin Oncol. 2010;28:2280–5.CrossRefGoogle Scholar
  71. 71.
    Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA. 2008;300:2277–85.CrossRefGoogle Scholar
  72. 72.
    Moore RA, Adel N, Riedel E, Bhutani M, Feldman DR, Tabbara NE, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol. 2011;29:3466–73.CrossRefGoogle Scholar
  73. 73.
    De Forni M, Bugat R, Sorbette F, Delay M, Bachaud JM, Chevreau C. Cardiotoxicity of continuous intravenous infusion of 5-fluorouracil: clinical study, prevention and physiopathology. Apropos of 13 cases. Bull Cancer. 1990;77:429–38. [Article in French]Google Scholar
  74. 74.
    Südhoff T, Enderle MD, Pahlke M, Petz C, Teschendorf C, Graeven U, Schmiegel W. 5-fluorouracil induces arterial vasocontractions. Ann Oncol. 2004;15:661–4.CrossRefGoogle Scholar
  75. 75.
    Polk A, Vistisen K, Vaage-Nilsen M, Nielsen DL. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharmacol Toxicol. 2014;15:47.  https://doi.org/10.1186/2050-6511-15-47.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Rowinsky EK, McGuire WP, Guarnieri T, Fisherman JS, Christian MC, Donehower RC. Cardiac disturbances during the administration of taxol. J Clin Oncol. 1991;9:1704–12.CrossRefGoogle Scholar
  77. 77.
    Schrader C, Keussen C, Bewig B, von Freier A, Lins M. Symptoms and signs of an acute myocardial ischemia caused by chemotherapy with Paclitaxel (Taxol) in a patient with metastatic ovarian carcinoma. Eur J Med Res. 2005;10:498–501.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and redisposing factors. Cancer Treat Rev. 2013;39:974–84.  https://doi.org/10.1016/j.ctrv.2013.03.005.CrossRefGoogle Scholar
  79. 79.
    Dixon A, Nakamura JM, Oishi N, Wachi DH, Fukuyama O. Angina pectoris and therapy with cisplatin, vincristine, and bleomycin. Ann Intern Med. 1989;111:342–3.CrossRefGoogle Scholar
  80. 80.
    Rodriguez J, Collazos J, Gallardo M, Hernando G. Angina pectoris following cisplatin, etoposide, and bleomycin in a patient with advanced testicular cancer. Ann Pharmacother. 1995;29:138–9.CrossRefGoogle Scholar
  81. 81.
    Fukuda M, Oka M, Itoh N, Sakamoto T, Mori H, Hayakawa A, Kohno S. Vasospastic angina likely related to cisplatin-containing chemotherapy and thoracic irradiation for lung cancer. Intern Med. 1999;38:436–8.CrossRefGoogle Scholar
  82. 82.
    Stefenelli T, Kuzmits R, Ulrich W, Glogar D. Acute vascular toxicity after combination chemotherapy with cisplatin, vinblastine, and bleomycin for testicular cancer. Eur Heart J. 1988;9:552–6.CrossRefGoogle Scholar
  83. 83.
    Schwarzer S, Eber B, Greinix H, Lind P. Non-Q-wave myocardial infarction associated with bleomycin and etoposide chemotherapy. Eur Heart J. 1991;12:748–50.PubMedGoogle Scholar
  84. 84.
    Gallagher H, Carroll WM, Dowd M, Rochev Y. The effects of vinblastine on endothelial cells. Endothelium. 2008;15:9–15.  https://doi.org/10.1080/10623320802092161.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Lu JI, Carhart RL, Graziano SL, Gajra A. Acute coronary syndrome secondary to fluorouracil infusion. J Clin Oncol. 2006;24:2959–60.  https://doi.org/10.1200/JCO.2005.04.0766.CrossRefPubMedGoogle Scholar
  86. 86.
    Cardinale D, Colombo A, Colombo N. Acute coronary syndrome induced by oral capecitabine. Can J Cardiol. 2006;22:251–3.CrossRefGoogle Scholar
  87. 87.
    Frickhofen N, Beck FJ, Jung B, Fuhr HG, Andrasch H, Sigmund M. Capecitabine can induce acute coronary syndrome similar to 5-fluorouracil. Ann Oncol. 2002;13:797–801.CrossRefGoogle Scholar
  88. 88.
    Ozturk B, Tacoy G, Coskun U, Yaman E, Sahin G, Buyukberber S, et al. Gemcitabine-induced acute coronary syndrome: a case report. Med Princ Pract. 2009;18:76–80.  https://doi.org/10.1159/000163051.CrossRefPubMedGoogle Scholar
  89. 89.
    Armitage JD, Montero C, Benner A, Armitage JO, Bociek G. Acute coronary syndromes complicating the first infusion of rituximab. Clin Lymphoma Myeloma. 2008;8:253–5.  https://doi.org/10.3816/CLM.2008.n.035.CrossRefPubMedGoogle Scholar
  90. 90.
    Ito D, Shiraishi J, Nakamura T, Maruyama N, Iwamura Y, Hashimoto S, et al. Primary percutaneous coronary intervention and intravascular ultrasound imaging for coronary thrombosis after cisplatin-based chemotherapy. Heart Vessel. 2012;27:634–8.  https://doi.org/10.1007/s00380-011-0222-5.CrossRefGoogle Scholar
  91. 91.
    Berliner S, Rahima M, Sidi Y, Teplitsky Y, Zohar Y, Nussbaum B, et al. Acute coronary events following cisplatin-based chemotherapy. Cancer Investig. 1990;8(6):583–6.CrossRefGoogle Scholar
  92. 92.
    Jafri M, Protheroe A. Cisplatin-associated thrombosis. Anti-Cancer Drugs. 2008;19:927–9.  https://doi.org/10.1097/CAD.0b013e3283100e9c.CrossRefPubMedGoogle Scholar
  93. 93.
    Karabay KO, Yildiz O, Aytekin V. Multiple coronary thrombi with cisplatin. J Invasive Cardiol. 2014;26:E18–20.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Doll DC, List AF, Greco FA, Hainsworth JD, Hande KR, Johnson DH. Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ-cell tumors of the testis. Ann Intern Med. 1986;105:48–51.CrossRefGoogle Scholar
  95. 95.
    Panella M, Ross JE, Garvin K, Martin A. Cardiac sudden death as a result of acute coronary artery thrombosis during chemotherapy for testicular carcinoma. J Forensic Sci. 2010;55:1384–8.  https://doi.org/10.1111/j.1556-4029.2010.01437.x.CrossRefPubMedGoogle Scholar
  96. 96.
    Togna GI, Togna AR, Franconi M, Caprino L. Cisplatin triggers platelet activation. Thromb Res. 2000;99:503–9.CrossRefGoogle Scholar
  97. 97.
    Dieckmann KP, Gerl A, Witt J, Hartmann JT. German Testicular Cancer Study Group. Myocardial infarction and other major vascular events during chemotherapy for testicular cancer. Ann Oncol. 2010;21:1607–11.  https://doi.org/10.1093/annonc/mdp597.CrossRefPubMedGoogle Scholar
  98. 98.
    Gietema JA, Meinardi MT, Messerschmidt J, Gelevert T, Alt F, Uges DR, Sleijfer DT. Circulating plasma platinum more than 10 years after cisplatin treatment for testicular cancer. Lancet. 2000;355:1075–6.CrossRefGoogle Scholar
  99. 99.
    Smith SA, Auseon AJ. Chemotherapy-induced takotsubo cardiomyopathy. Heart Fail Clin. 2013;9:233–42., x.  https://doi.org/10.1016/j.hfc.2012.12.009.CrossRefPubMedGoogle Scholar
  100. 100.
    Dechant C, Baur M, Böck R, Czejka M, Podczeck-Schweighofer A, Dittrich C, et al. Acute reversible heart failure caused by coronary vasoconstriction due to continuous 5-fluorouracil combination chemotherapy. Case Rep Oncol. 2012;5:296–301.  https://doi.org/10.1159/000339573.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Qasem A, Bin Abdulhak AA, Aly A, Moormeier J. Capecitabine-induced Takotsubo cardiomyopathy: a case report and literature review. Am J Ther. 2016;23(5):e1188–92.CrossRefGoogle Scholar
  102. 102.
    Gianni M, Dentali F, Lonn E. 5 fluorouracil-induced apical ballooning syndrome: a case report. Blood Coagul Fibrinolysis. 2009;20:306–8.  https://doi.org/10.1097/MBC.0b013e328329e431.CrossRefPubMedGoogle Scholar
  103. 103.
    Numico G, Sicuro M, Silvestris N, Mozzicafreddo A, Trogu A, Malossi A, et al. Takotsubo syndrome in a patient treated with sunitinib for renal cancer. J Clin Oncol. 2012;30:e218–20.  https://doi.org/10.1200/JCO.2012.42.4911.CrossRefPubMedGoogle Scholar
  104. 104.
    Baumann S, Huseynov A, Goranova D, Faust M, Behnes M, Nolte F, et al. Takotsubo cardiomyopathy after systemic consolidation therapy with high-dose intravenous cytarabine in a patient with acute myeloid leukemia. Oncol Res Treat. 2014;37:487–90.  https://doi.org/10.1159/000365536.CrossRefPubMedGoogle Scholar
  105. 105.
    Ovadia D, Esquenazi Y, Bucay M, Bachier CR. Association between takotsubo cardiomyopathy and axitinib: case report and review of the literature. J Clin Oncol. 2015;33:e1–3.  https://doi.org/10.1200/JCO.2013.48.7280.CrossRefPubMedGoogle Scholar
  106. 106.
    Franco TH, Khan A, Joshi V, Thomas B. Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer. Ther Clin Risk Manag. 2008;4:1367–70.CrossRefGoogle Scholar
  107. 107.
    Ng KH, Dearden C, Gruber P. Rituximab-induced Takotsubo syndrome: more cardiotoxic than it appears? BMJ Case Rep. 2015;2015  https://doi.org/10.1136/bcr-2014-208203.Google Scholar
  108. 108.
    Khanji M, Nolan S, Gwynne S, Pudney D, Ionescu A. Tako-Tsubo syndrome after trastuzumab – an unusual complication of chemotherapy for breast cancer. Clin Oncol (R Coll Radiol). 2013;25:329.  https://doi.org/10.1016/j.clon.2012.12.007.CrossRefGoogle Scholar
  109. 109.
    Bhakta S, Flick SM, Cooney MM, Greskovich JF, Gilkeson RC, Remick SC, et al. Myocardial stunning following combined modality combretastatin-based chemotherapy: two case reports and review of the literature. Clin Cardiol. 2009;32:E80–4.  https://doi.org/10.1002/clc.20685.CrossRefPubMedGoogle Scholar
  110. 110.
    Vejpongsa P, Banchs J, Reyes M, Iliescu G, Akinyemi M, Yusuf S, et al. Takotsubo cardiomyopathy in cancer patients: triggers, recovery, and resumption of therapy. J Am Coll Cardiol. 2015;65:A927.CrossRefGoogle Scholar
  111. 111.
    Kobayashi N, Hata N, Yokoyama S, Shinada T, Shirakabe A, Mizuno K. A case of Takotsubo cardiomyopathy during 5-fluorouracil treatment for rectal adenocarcinoma. J Nippon Med Sch. 2009;76:27–33.CrossRefGoogle Scholar
  112. 112.
    Stewart T, Pavlakis N, Ward M. Cardiotoxicity with 5-fluorouracil and capecitabine: more than just vasospastic angina. Intern Med J. 2010;40:303–7.  https://doi.org/10.1111/j.1445-5994.2009.02144.x.CrossRefPubMedGoogle Scholar
  113. 113.
    Grunwald MR, Howie L, Diaz LA Jr. Takotsubo cardiomyopathy and fluorouracil: case report and review of the literature. J Clin Oncol. 2012;30:e11–4.  https://doi.org/10.1200/JCO.2011.38.5278.CrossRefPubMedGoogle Scholar
  114. 114.
    Staff S, Lagerstedt E, Seppänen J, Mäenpää J. Acute digital ischemia complicating gemcitabine and carboplatin combination chemotherapy for ovarian cancer. Acta Obstet Gynecol Scand. 2011;90:1296–7.  https://doi.org/10.1111/j.1600-0412.2011.01259.x.CrossRefPubMedGoogle Scholar
  115. 115.
    Vogelzang NJ, Bosl GJ, Johnson K, Kennedy BJ. Raynaud’s phenomenon: a common toxicity after combination chemotherapy for testicular cancer. Ann Intern Med. 1981;95:288–92.CrossRefGoogle Scholar
  116. 116.
    Kuhar CG, Mesti T, Zakotnik B. Digital ischemic events related to gemcitabine: report of two cases and a systematic review. Radiol Oncol. 2010;44:257–61.  https://doi.org/10.2478/v10019-010-0020-1.CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Zeidman A, Dicker D, Mittelman M. Interferon-induced vasospasm in chronic myeloid leukaemia. Acta Haematol. 1998;100:94–6.CrossRefGoogle Scholar
  118. 118.
    McGrath SE, Webb A, Walker-Bone K. Bleomycin-induced Raynaud’s phenomenon after single-dose exposure: risk factors and treatment with intravenous iloprost infusion. J Clin Oncol. 2013;31:e51–2.  https://doi.org/10.1200/JCO.2012.43.2872.CrossRefPubMedGoogle Scholar
  119. 119.
    Raanani P, Ben-Bassat I. Immune-mediated complications during interferon therapy in hematological patients. Acta Haematol. 2002;107:133–44. doi: 57631.CrossRefGoogle Scholar
  120. 120.
    Madabhavi I, Revannasiddaiah S, Rastogi M, Gupta MK. Paraneoplastic Raynaud’s phenomenon manifesting before the diagnosis of lung cancer. BMJ Case Rep. 2012;2012  https://doi.org/10.1136/bcr.03.2012.5985.Google Scholar
  121. 121.
    Stefan O, Vera N, Otto B, Heinz L, Wolfgang G. Stroke in cancer patients: a risk factor analysis. J Neuro-Oncol. 2009;94:221–6.  https://doi.org/10.1007/s11060-009-9818-3.CrossRefGoogle Scholar
  122. 122.
    Sanon S, Lenihan DJ, Mouhayar E. Peripheral arterial ischemic events in cancer patients. Vasc Med. 2011;16:119–30.  https://doi.org/10.1177/1358863X10388346.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Ahn D, Brickner ME, Dowell J. Embolic stroke secondary to an indwelling catheter in a patient with a patent foramen ovale: a case report and review of the literature. Clin Adv Hematol Oncol. 2012;10:335–7.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Chaturvedi S, Ansell J, Recht L. Should cerebral ischemic events in cancer patients be considered a manifestation of hypercoagulability? Stroke. 1994;25:1215–8.CrossRefGoogle Scholar
  125. 125.
    Rogers LR. Cerebrovascular complications in patients with cancer. Semin Neurol. 2010;30:311–9.  https://doi.org/10.1055/s-0030-1255224.CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    El Amrani M, Heinzlef O, Debroucker T, Roullet E, Bousser MG, Amarenco P. Brain infarction following 5-fluorouracil and cisplatin therapy. Neurology. 1998;51:899–901.CrossRefGoogle Scholar
  127. 127.
    Serrano-Castro PJ, Guardado-Santervás P, Olivares-Romero J. Ischemic stroke following cisplatin and 5-fluorouracil therapy: a transcranial Doppler study. Eur Neurol. 2000;44:63–4.  https://doi.org/10.1159/000008197.CrossRefGoogle Scholar
  128. 128.
    Meattini I, Scotti V, Pescini F, Livi L, Sulprizio S, Palumbo V, et al. Ischemic stroke during cisplatin-based chemotherapy for testicular germ cell tumor: case report and review of the literature. J Chemother. 2010;22:134–6.  https://doi.org/10.1179/joc.2010.22.2.134.CrossRefGoogle Scholar
  129. 129.
    Periard D, Boulanger CM, Eyer S, Amabile N, Pugin P, Gerschheimer C, et al. Are circulating endothelial-derived and platelet-derived microparticles a pathogenic factor in the cisplatin-induced stroke? Stroke. 2007;38:1636–8.  https://doi.org/10.1161/STROKEAHA.106.479733.CrossRefPubMedGoogle Scholar
  130. 130.
    Martín GG, Fernández SP, Castro VS, Cueto OH, Acebal MR. Vertebral artery occlusion after chemotherapy. Stroke. 2008;39:e38.; author reply e39.  https://doi.org/10.1161/STROKEAHA.107.503987.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Valentina Mercurio
    • 1
  • Giulio Agnetti
    • 2
    • 3
  • Pasquale Pagliaro
    • 4
  • Carlo G. Tocchetti
    • 5
  1. 1.Division of Pulmonary and Critical Care MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.DIBINEMUniversity of BolognaBolognaItaly
  4. 4.Clinical and Biological SciencesAOU San Luigi GonzagaOrbassanoItaly
  5. 5.Department of Translational Medical SciencesFederico II UniversityNaplesItaly

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