Cardiac toxicity of fluoropyrimidines in the treatment of solid gastrointestinal tumors

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Acesso é pago ou somente para assinantes

Resumo

Background. Fluoropyrimidines are highly effective and commonly prescribed anticancer drugs that are used in a wide range of chemotherapy (CT) regimens to treat various types of cancer. Their cardiac toxicity is not only a life-threatening complication, but also leads to the rejection of effective chemotherapy, thereby reducing the life expectancy of patients.

Methods. A cohort of 16 patients with various types of solid gastrointestinal tumors, treated with fluoropyrimidines with detected cardiotoxicity was selected. All patients received treatment at the N.N. Blokhin National Medical Research Institute of Oncology from February 2021 to February 2022.

Results. The most common symptoms of cardiotoxicity included dyspnea, retrosternal pain, and short-term loss of consciousness. An increase in the blood troponin I and NTproBNP levels was registered in 4 patients. In 56% of patients, cardiotoxicity was noted during the first course of treatment. In 1 (6.25%) of 16 cases, a fatal outcome was registered: sudden death during the first infusion of fluorouracil (5-FU).

Conclusion. Patients treated with fluoropyrimidines should be closely monitored and 5-FU should be discontinued at the first sign of cardiovascular toxicity. Re-administration of fluoropyrimidines is not recommended unless they significantly improve the prognosis; but after careful examination of the cardiovascular system, prophylaxis under close monitoring against the background of enhanced cardiac therapy, it is worth considering switching to a bolus of 5-FU. Recognition of risk factors for fluoropyrimidine-associated cardiotoxicity even before the start of chemotherapy is necessary, since it allows either to reduce their influence or to enhance control to detect complications at an early stage.

Texto integral

Acesso é fechado

Sobre autores

L. Bogatyreva

N.I. Pirogov Russian National Research Medical University

Email: besovans@mail.ru
ORCID ID: 0009-0008-6440-9960
Rússia, Moscow

Natalia Besova

N.N. Blokhin National Medical Research Institute of Oncology

Autor responsável pela correspondência
Email: besovans@mail.ru
ORCID ID: 0000-0002-1693-0523

Cand. Sci. (Med.), Leading Researcher at the Department of Antitumor Drug Therapy № 2, Division of Drug Treatment

Rússia, Moscow

G. Yunayev

N.N. Blokhin National Medical Research Institute of Oncology

Email: besovans@mail.ru
ORCID ID: 0000-0002-9562-9113
Rússia, Moscow

I. Kurmukov

N.N. Blokhin National Medical Research Institute of Oncology

Email: besovans@mail.ru
ORCID ID: 0000-0001-8463-2600
Rússia, Moscow

E. Obarevich

N.N. Blokhin National Medical Research Institute of Oncology

Email: besovans@mail.ru
ORCID ID: 0000-0001-9885-3922
Rússia, Moscow

D. Gavrilova

N.N. Blokhin National Medical Research Institute of Oncology

Email: besovans@mail.ru
ORCID ID: 0009-0008-5996-6965
Rússia, Moscow

A. Egorova

N.I. Pirogov Russian National Research Medical University

Email: besovans@mail.ru
ORCID ID: 0000-0003-3904-8530
Rússia, Moscow

N. Lepkova

N.I. Pirogov Russian National Research Medical University

Email: besovans@mail.ru
ORCID ID: 0000-0002-5890-6273
Rússia, Moscow

A. Tryakin

N.N. Blokhin National Medical Research Institute of Oncology

Email: besovans@mail.ru
ORCID ID: 0000-0003-2245-214X
Rússia, Moscow

Bibliografia

  1. Luis Z.J., Lancellotti P., Munoz D.R., et al. ESC Scientific Document Group, 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 Heart J. 2016;37(36):768–2801. doi: 10.1093/eurheartj/ehw211.
  2. Jurczyk M., Krol M., Midro A., et al. Cardiotoxicity of Fluoropyrimidines: Epidemiology, Mechanisms, Diagnosis, and Management. J Clin Med. 2021;10(19):4426. doi: 10.3390/jcm10194426.
  3. Meyer C.C., Calis K.A., Burke L.B., et.al., Symptomatic cardiotoxicity associated with 5-fluorouracil. Pharmacother. 1997; 17(4):729–36.
  4. Jin, X., Bai, Y., Gao, L., et al. Incidence of and risk factors for cardiotoxicity after fluorouracil-based chemotherapy in locally advanced or metastatic gastric cancer patients. Cancer Chemother Pharmacol. 2019;84:599–607. doi: 10.1007/s00280-019-03888-1.
  5. Jensen S.A., Sorensen J.B. Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine. Cancer Chemother Pharmacol. 2006;58:487–93. doi: 10.1007/s00280-005-0178-1.
  6. Koca D., Salman T., Unek I., et al. Clinical and Electrocardiography Changes in Patients Treated with Capecitabine. Chemother. 2011;57:381–87. doi: 10.1159/000331645.
  7. Коломиец Е.А., Бесова Н.С., Курмуков И.А. и др. Кардиоваскулярная токсичность фторпиримидинов. Фарматека. 2017;18(351):76–9. [Kolomiets E.A., Besova N.S, Kurmukov I.A., et al. Cardiovascular toxicity of fluoropyrimidines. Farmateka. 2017;18(351):76–9. (In Russ.)].
  8. de Forni M., Malet-Martino M.C., Jaillais P., et al. Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J Clin Oncol. 1992;10(11):1795–801. doi: 10.1200/JCO.1992.10.11.1795.
  9. Lombardi P., Aimar G., Peraldo-Neia, et al. Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: a prospective observational trial (CHECKPOINT). Oncol Rep. 2023;49:31. doi: 10.3892/or.2022.8468.
  10. Li M., Kroetz D.L. Bevacizumab-induced hypertension: Clinical presentation and molecular understanding. Pharmacol Ther. 2018;182:152–60. doi: 10.1016/j.pharmthera.2017.08.012.
  11. Ranpura V., Pulipati B., Chu D., et al. Increased risk of high-grade hypertension with bevacizumab in cancer patients: a meta-analysis. Am J Hypertens. 2010;23(5):460–68. doi: 10.1038/ajh.2010.25.
  12. Mal G.S., Artyushkova E.B., Bykanova A.M., et al. Bevacizumab-Induced arterial hypertensis problems as the event of cardiotoxicity in colorectal racs patients. Mod Probl Sci Educat. 2022;4. doi: 10.17513/spno.31949.
  13. Saif M.W., Shah M.M., Shah A.R. Fluoropyrimidine-associated cardiotoxicity: revisited. Expert Opin Drug Saf. 2009;8(2):191–202. doi: 10.1517/14740330902733961.
  14. Dyhl-Polk A., Schou M., Vistisen K.K., et al. Myocardial Ischemia Induced by 5-Fluorouracil: A Prospective Electrocardiographic and Cardiac Biomarker Study. Oncologist. 2021;26(3):e403–13. doi: 10.1002/onco.13536.
  15. Kosmas C., Kallistratos M.S., Kopterides P., et al. Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol. 2008;134.75–82. doi: 10.1007/s00432-007-0250-9
  16. Płonska-Gosciniak E., Rozżewicz M., Kasprzak J., et al. Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study. Kardiol Pol. 2017;75(2):150–56. doi: 10.5603/KP.a2016.0163.
  17. Amraotkar A.R., Pachika A., Grubb K.J., et al. Rapid Extracorporeal Membrane Oxygenation Overcomes Fulminant Myocarditis Induced by 5-Fluorouracil. Tex Heart Inst J. 2016;43(2):178–82. doi: 10.14503/THIJ-15-5100.
  18. Joy G., Eissa H., Karoudi R.Al., et al. Fluorouracil-induced Takotsubo cardiomyopathy causing cardiogenic shock: a case report of clinical and acute cardiac magnetic resonance imaging features. Eur Heart J Case Rep. 2019;3(4):1–6. doi: 10.1093/ehjcr/ytz146.
  19. Sundaravel S., Alrifai A., Kabach M., et al. «FOLFOX Induced Takotsubo Cardiomyopathy Treated with Impella Assist Device». Case Rep Cardiol. 2017;2017(Article ID 8507096):4. doi: 10.1155/2017/8507096.
  20. Ray J., Mahmood A., Dogar M., et al. “Simultaneous Cardiotoxicity and Neurotoxicity Associated with 5-fluorouracil Containing Chemotherapy: A Case Report and Literature Review.” Am J Med Case Rep. 2020;8(3):73–5. Doi: 10.12691/ ajmcr-8-3-2.
  21. Kinhult S., Albertsson M., Eskilsson J., et al. Effects of probucol on endothelial damage by 5-fluorouracil. Acta Oncol. 2003;42(4):304–8. doi: 10.1080/02841860310004409.
  22. Tsibiribi P., Bui-Xuan C., Bui-Xuan B., et al. Cardiac lesions induced by 5-fluorouracil in the rabbit. Hum Exp Toxicol. 2006;25(6):305–9. doi: 10.1191/0960327106ht628oa.
  23. Kinhult S., Albertsson M., Eskilsson J., et al. Antithrombotic treatment in protection against thrombogenic effects of 5-fluorouracil on vascular endothelium: a scanning microscopy evaluation. Scanning. 2001;23(1):1–8. doi: 10.1002/sca.4950230101.
  24. Cwikiel M., Zhang B., Eskilsson J., et al. The influence of 5-fluorouracil on the endothelium in small arteries. An electron microscopic study in rabbits. Scanning Microsc. 1995;9(2):561–76.
  25. Cwikiel M., Eskilsson J., Wieslander J.B., et al. The appearance of endothelium in small arteries after treatment with 5-fluorouracil. An electron microscopic study of late effects in rabbits. Scanning Microsc. 1996;10(3):805–18; discussion 819.
  26. Cardinale D., Colombo A., Colombo N. Acute coronary syndrome induced by oral capecitabine. Can J Cardiol. 2006;22(3):251–53. doi: 10.1016/s0828-282x(06)70905-9.
  27. Scott P.A., Ferchow L., Hobson A., et al. Coronary spasm induced by capecitabine mimicks ST elevation myocardial infarction. Emerg Med J. 2008;25(10):699–700. doi: 10.1136/emj.2008.060574.
  28. Tajik R., Saadat H., Taherkhani M., et al. Angina induced by 5-fluorouracil infusion in a patient with normal coronaries. Am Heart Hosp J. 2010;8(2):E111–12. doi: 10.15420/ahhj.2010.8.2.111.
  29. Atar A., Korkmaz M.E., Ozin B. Two cases of coronary vasospasm induced by 5-fluorouracil. Anadolu Kardiyol Derg. 2010;10(5):461–62. doi: 10.5152/akd.2010.147.
  30. Calık A.N., Celiker E., Velibey Y., et al. Effect of initial dose of 5-fluorouracil: rapid improvement in severe, acute toxic myopericarditis. Am J Emerg Med. 2012;30(1):257.e1–3. doi: 10.1016/j.ajem.2010.10.025.
  31. Basselin C., Fontanges T., Descotes J., et al. 5-Fluorouracil-induced Tako-Tsubo-like syndrome. Pharmacother. 2011;31(2):226. doi: 10.1592/phco.31.2.226.
  32. Prandoni P., Falanga A., Piccioli A. Cancer and venous thromboembolism. Lancet Oncol. 2005;6(6):401–10. doi: 10.1016/S1470-2045(05)70207-2.
  33. Shoemaker L.K., Arora U., Rocha Lima C.M. 5-fluorouracil-induced coronary vasospasm. Cancer Control. 2004;11(1):46–9. doi: 10.1177/107327480401100207.
  34. Schnetzler B., Popova N., Collao Lamb C., et al. Coronary spasm induced by capecitabine. Ann Oncol. 2001;12(5):723–24. doi: 10.1023/a:1011152931300.
  35. Mafrici A., Alberti A., Corrada E., et al. Management of patients with persistent chest pain and ST-segment elevation during 5-fluorouracil treatment: report about two cases. Ital Heart J. 2003;4(12):895–99.
  36. Luwaert R.J., Descamps O., Majois F., et al. Coronary artery spasm induced by 5-fluorouracil. Eur. Heart J. 1991;12(3):468–70. doi: 10.1093/oxfordjournals.eurheartj.a059919. [PMID: 2040332].
  37. Alter P., Herzum M., Soufi M., et al. Cardiotoxicity of 5-fluorouracil. Cardiovasc Hematol Agents Med Chem. 2006;4(1):1–5. doi: 10.2174/187152506775268785.
  38. Salepci T., Seker M., Uyarel H., et al. 5-Fluorouracil induces arterial vasoconstrictions but does not increase angiotensin II levels. Med Oncol. 2010;27(2):416–20. doi: 10.1007/s12032-009-9226-8.
  39. Sudhoff T., Enderle M.D., Pahlke M., et al. Teschendorf C, Graeven U, Schmiegel W. 5-Fluorouracil induces arterial vasocontractions. Ann Oncol. 2004;15(4):661–64. doi: 10.1093/annonc/mdh150.
  40. Mosseri M., Fingert H.J., Varticovski L., et al. In vitro evidence that myocardial ischemia resulting from 5-fluorouracil chemotherapy is due to protein kinase C-mediated vasoconstriction of vascular smooth muscle. Cancer Res. 1993;53:3028–33.
  41. Polk A., Vaage-Nilsen M., Vistisen K., et al.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. doi: 10.1016/j.ctrv.2013.03.005.
  42. Rateesh S., Luis S.A., Luis C.R., et al. Myocardial infarction secondary to 5-fluorouracil: not an absolute contraindication to rechallenge? Int J Cardiol. 2014;172:e331–33.
  43. Poltavskaya M.G. Correction of cardiotoxic in oncological patients. 2021. Infomedfarm Dialog info@imfd.ru imfd.ru’2021/06/25/korrkardioyonkolpashient.
  44. Коломиец Е.А., Курмуков И.А., Кашия Ш.Р. и др. Острый инфаркт миокарда в отсутствии обструкции коронарных артерий - осложнение противоопухолевой терапии капецитабином. Рациональная Фармакотерапия в Кардиологии. 2017;13(6):813–818. [Kolomiets E.A., Kurmukov I.A., Besova N.S., et al. Acute Myocardial Infarction in the Absence of Coronary Artery Obstruction – a Complication of Anticancer Therapy with Capecitabine. Ratsional’naya Farmakoterapiya v Kardiologii. 2017;13(6):813–18. (In Russ.). doi: 10.20996/1819-6446-2017-13-6-813-818.
  45. Ambrosy A.P., Kunz P.L., Fisher G.A., et al. Capecitabine-induced chest pain relieved by diltiazem. Am J Cardiol. 2012;110(11):1623–26. doi: 10.1016/j.amjcard.2012.07.026.
  46. Jurczyk M., Krol M., Midro A., et al. Cardiotoxicity of Fluoropyrimidines: Epidemiology, Mechanisms, Diagnosis, and Management. J Clin Med. 2021;10(19):4426. doi: 10.3390/jcm10194426.
  47. Punt C.J.A., Kwakman J.J.M., et al. PLCRC working group. Long-Term Safety Data on S-1 Administered After Previous Intolerance to Capecitabine-Containing Systemic Treatment for Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2022;21(3):229–35. doi: 10.1016/j.clcc.2022.02.004.

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML

Este site utiliza cookies

Ao continuar usando nosso site, você concorda com o procedimento de cookies que mantêm o site funcionando normalmente.

Informação sobre cookies