PharmatecaPharmatecaФарматека2073-40342414-9128Bionika Media290024ArticlesСтатьиResearch ArticleCardiovascular toxicity of fluoropirymidinesКардиоваскулярная токсичность фторпиримидиновKolomietsE. AКоломиецЕ. А

cardiologisT., an advisory group of the Department of Hospital Therapy and Functional Diagnostics of the Department of Functional Diagnostics, Intensive Care and Rehabilitation

врач-кардиолог, консультативная группа отделения госпитальной терапии и функциональной диагностики отдела функциональной диагностики, интенсивной терапии и реабилитации

dr.kolomiets@mail.ruBesovaN. SБесоваН. СKurmukovI. AКурмуковИ. АKashiaSh. RКашияШ. РNarimanovM. NНаримановМ. НSandomirskayaA. PСандомирскаяА. ПFSBI NMRC of Oncology n.a. N.N. Blokhin of RMHФГБУ НМИЦ онкологии им. Н.Н. Блохина Минздрава РФ200920172418NO18 (2017)№18 (2017)767926022023Copyright ©; 2017, Bionika MediaCopyright ©; 2017, ООО «Бионика Медиа»2017Bionika MediaООО «Бионика Медиа»https://journals.eco-vector.com/2073-4034/article/view/290024

Cardiovascular toxicity of fluoropyrimidines is revealed in 1-19% of patients. Its frequency consistently increases with the administration of large single doses and long-term infusions, in case of combination with bevacizumab and platinum preparations; with concomitant coronary artery disease, in former smokers. Due to multiple pathophysiological mechanisms of damage to the heart and vessels, the manifestations of cardiovascular toxicity are diverse. The severity of the damage varies from asymptomatic changes in the electrocardiogram and arrhythmia to acute coronary syndrome and sudden death. The review describes the diagnostic algorithm and possible approaches to the treatment and prevention of repeated cardiovascular events associated with the use of fluoropyrimidines.

Кардиоваскулярная токсичность фторпиримидинов выявляется у 1-19% пациентов. Частота закономерно возрастает при введении больших разовых доз, проведении длительных инфузий, сочетании с бевацизумабом и препаратами платины; при сопутствующей ишемической болезни сердца, у пациентов с анамнезом табакокурения. В связи с множественными патофизиологическими механизмами повреждения сердца и сосудов проявления кардиоваскулярной токсичности разнообразны. Тяжесть повреждения варьируется от бессимптомных изменений электрокардиограммы и аритмии до острого коронарного синдрома и внезапной смерти. В обзоре описывается алгоритм диагностики и возможные подходы к лечению и профилактике повторных кардиоваскулярных событий, связанных с применением фторпиримидинов.

fluoropyrimidinesfluorouracilcapecitabinecardiotoxicityacute coronary syndromearrhythmiacoronary artery diseaseфторпиримидиныфторурацилкапецитабинкардиотоксичностьострый коронарный синдромаритмияишемическая болезнь сердцаMarwick T.H. Cancer Therapy-Related Cardiac Dysfunction: Unresolved Issues. Can. J. Cardiol. 2016;32:842-46.Layoun M.E., Wickramasinghe C.D., Peralta M.V., Yang E.H. Fluoropyrimidine-Induced Cardiotoxicity: Manifestations, Mechanisms, and Management © Springer Science+Business Media New York. 2016.Lokich J.J. Infusional 5-FU: historical evolution, rationale, and clinical experience. Oncology. 1998;12:19-22.Anand A. Fluorouracil cardiotoxicity. Ann. Pharmacother. 1994;28:374.Akhtar S., Salim K., Bano Z. Symptomatic cardiotoxicity with high dose 5-fluorouracil infusion: a prospective study. Oncology. 1993;50:441.Wacker A., Lersch C., Scherpinski U., Reindl L., Seyfarth M. High incidence of angina pectoris in patients treated with 5-fluorouracil: a planned surveillance study with 102 patients. Oncology. 2003;65(2):108-12.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):151-56.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 predisposing factors. Cancer Treat. Rev. 2013;39(8):974-84.Suter T.M., Ewer M.S. Cancer drugs and the heart: importance and management. Eur. Heart J. 2013;34:1102-11.Labianca R., Beretta G., Clerici M., Fraschini P., Luporini G. Cardiac toxicity of 5-FU: a study of 1,083 patients. Tumori. 1982;68:505-10.De Forni M. Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J. Clin. Oncol. 1992;10(11): 1795-801.Meyer C.C., Calis K.A., Burke L.B., Walawander C.A., Grasela T.H. Symptomatic cardiotoxicity associated with 5-fluorouracil. Pharmacotherapy. 1997;17(4):729-36.Khichina E., Kashiya S., Sandomirskaya A., Kurmukov I., Obukhova O., Davydova L., Goncharova Y. European Journal of Preventive Cardiology. 2017;24(Suppl. 1):26-7.Кашия Ш.Р, Курмуков И.А., Гончарова Ю.К., Зипалова Л.В., Хичина Е.А. Распространенность сердечно-сосудистой патологии у онкологических больных, получающих противоопухолевое лекарственное лечение в специализированном стационаре. Злокачественные опухоли. 2016; 4(Suppl.1, 20):275.Jensen S.A., Sаrensen J.B. Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine. Cancer Chemother. Pharmacol. 2006;58(4):487-93.Becker K., Erckenbrecht J.F., Haussinger D., et al. Cardiotoxicity of the antiproliferative compound fluorouracil. Drugs. 1999;57:475-84.Sorrentino M.F., KimJ.,Foderaro A.E., Truesdell A.G. 5-fluorouracil induced cardiotoxicity: review of the literature. Cardiol. J. 2012;19(5):453-58.Ng M., Cunningham D., Norman A.R. 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;41:1542-46.Lamberti M., Porto S., Marra M., Zappavigna S., Grimaldi A., Feola D., Pesce D., Naviglio S., Spina A., Sannolo N., Caraglia M. 5-Fluorouracil induces apoptosis in rat cardiocytes through intracellular oxidative stress. J. Exp. Clin. Cancer Res. 2012;31:60-10.Durak I., Karaayvaz M., Kavutcu M., Cimen M.Y., Kacmaz M., Buyukkocak S., Ozturk HS. Reduced antioxidant defense capacity in myocardial tissue from guinea pigs treated with 5-fluorouracil. J. Toxicol. Environ. Health A. 2000;59:585-89.Schöber C., Papageorgiou E., Harstrick A., Bokemyer C., Mügge A., Stahl M. Cardiotoxicity of 5-fluorouracil in combination with folinic acid in patients with gastrointestinal cancer. Cancer 1993;72:2242-47.Daher I.N., Yeh E.T. Vascular complications of selected cancer therapies. Nat. Clin. Pract. Cardiovasc. Med. 2008;5:797-805.Soultati A., Mountzios G., Avgerinou C., Papaxoinis G., Pectasides D., Dimopoulos M.A., Papadimitriou C. Endothelial vascular toxicity from chemotherapeutic agents: preclinical evidence and clinical implications. Cancer Treat. Rev. 2012;38:473-83.Cameron A.C., Touyz R.M., Lang N.N. Vascular Complications of Cancer Chemotherapy (Review). Can. J. Cardiol. 2016;32:852-62.Alter P., Herzum M., Soufi M., Schaefer J.R., Maisch B. Cardiotoxicity of 5-fluorouracil. Cardiovasc. Hematol. Agents Med. Chem. 2006;4:1-5.Hurwitz H., Fehrenbacher L., Novotny W., et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 2004;350:2335-42.Meinardi M.T., Gietema J.A., van Veldhuisen D.J., van der Graaf W.T., de Vries E.G., Sleijfer D.T. Long-term chemotherapy-related cardiovascular morbidity. Cancer Treat. Rev. 2000;26:429-47.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.David J.S., Gueugniaud P.Y., Hepp A., Gaussorgues P., Petit P. Severe heart failure secondary to 5-fluorouracil and low-doses of folinic acid: usefulness of an intra-aortic balloon pump. Crit. Care Med. 2000;28(10):3558-60.Höllriegel R., Fischer J., Schuler G. Early extracorporeal membrane oxygenation support for 5-fluorouracil-induced acute heart failure with cardiogenic shock. Heart Views. 2014;15(1):26.Rateesh S., Shekar K., Naidoo R., Mittal D., Bhaskar B. Use of extracorporeal membrane oxygenation for mechanical circulatory support in a patient with 5-fluorouracil induced acute heart failure. Circ. Hear Fail. 2015;8(2):381-83.Tsavaris N., Kosmas C., Vadiaka M., et al. 5-fluorouracil cardiotoxicity is a rare, dose and schedule-dependent adverse event: a prospective study. J. BUON. 2005;10(2):205-11.Fontanella C., Aita M., Cinausero M., Aprile G., Baldin M.G., Dusi V. Capecitabine-induced cardiotoxicity: more evidence or clinical approaches to protect the patients heart? Onco. Targets Ther. 2014;7:1783-91.Rateesh S., Luis S.A., Luis C.R., Hughes B., Nicolae M. Myocardial infarction secondary to 5-fluorouracil: not an absolute contraindication to rechallenge? Int. J. Cardiol. 2014;172: e331-33.Cianci G., Morelli M.F., Cannita K., et al. Prophylactic options in patients with 5-fluorouracil-associated cardiotoxicity. Br. J. Cancer. 2003; 88:1507-509.Ambrosy A.P., Kunz P.L., Fisher G.A., Witteles R.M. Capecitabine-induced chest pain relieved by diltiazem. Am. J. Cardiol. 2012;110: 1623-26.