EVALUATION OF 5-FLUOROURACIL-INDUCED CARDIOTOXICITY: ROLE OF CARDIAC BIOMARKERS
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-1.17496Keywords:
5-fluorouracil, cardiac troponin I, cardiotoxicity, chemotherapy, gastrointestinal tumorsAbstract
Background: Side effects of chemotherapy in cancer patients need to be investigated in more detail. Aim: To determine the incidence of cardiotoxicity in patients treated with different chemotherapy regimens containing 5-fluorouracil (5-FU) in Zanjan, Iran. Patients and Methods: In a prospective cohort study, patients with different types of solid gastrointestinal tumors who were candidates for 5-FU based chemotherapy regimens were enrolled. The study population consisted of 100 patients (48 females and 52 males) with a mean age of 63.99 ± 12.40 years. We measured serum cardiac troponin I (cTnI) levels before and during each chemotherapy cycle and determined the occurrence of cardiotoxicity in patients based on the levels of cTnI, clinical signs and symptoms as well as electrocardiogram findings. In addition, we assessed a history of diabetes, hypertension, smoking, dyslipidemia and previous chest radiation as potential risk factors for cardiotoxicity. Results: The incidence of cardiotoxicity was 8%, of which 5 patients were diagnosed with acute coronary syndrome, 2 patients with arrhythmias and one with hypotension. In addition, there was no significant association between studied risk factors and 5-FU induced cardiotoxicity. Conclusion: The incidence of cardiotoxicity in patients receiving 5-FU infusion regimens was notable. Thus, paying more attention to the 5-FU-induced cardiotoxicity is necessary in order to improve the prognosis of patients with cancer.
References
Shakir DK, Rasul KI. Chemotherapy induced cardiomyopathy: pathogenesis, monitoring and management. J Clin Med Res 2009; 1: 8–12. https://doi.org/10.4021/jocmr2009.02.1225
Curigliano G, Cardinale D, Dent S, et al. Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA Cancer J Clin 2016; 66: 309-25. https://doi.org/10.3322/caac.21341
Cardinale D, Colombo A, Lamantia G, et al. Cardio-oncology: a new medical issue. Ecancermedicalscience 2008; 2: 126. https://doi.org/10.3332/ecancer.2008.126
Kalam K, Marwick TH. Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer 2013; 49: 2900–9. https://doi.org/10.1016/j.ejca.2013.04.030
Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR, Jr., et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J Am Coll Cardiol 2018; 71: 2281–90. https://doi.org/10.1016/j.jacc.2018.02.049
Chang VY, Wang JJ. Pharmacogenetics of chemotherapy-induced cardiotoxicity. Curr Oncol Rep 2018; 20: 52. https://doi.org/10.1007/s11912-018-0696-8
Cardinale D, Sandri MT. Role of biomarkers in chemotherapy-induced cardiotoxicity. Prog Cardiovasc Dis 2010; 53: 121–9. https://doi.org/10.1016/j.pcad.2010.04.002
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: 2355–62. https://doi.org/10.1016/j.jacc.2013.02.072
Tan L-L, Lyon AR. Role of biomarkers in prediction of cardiotoxicity during cancer treatment. Curr Treat Options Cardiovasc Med 2018; 20: 55. https://doi.org/10.1007/s11936-018-0641-z
Steger F, Hautmann MG, Kölbl O. 5-FU-induced cardiac toxicity — an underestimated problem in radiooncology? Radiat Oncol 2012; 7: 212. https://doi.org/10.1186/1748-717x-7-212
Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003; 3: 330–8. https://doi.org/10.1038/nrc1074
Sara JD, Kaur J, Khodadadi R, et al. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol 2018; 10: 1758835918780140-40. https://doi.org/10.1177/1758835918780140
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: 974–84. https://doi.org/10.1016/j.ctrv.2013.03.005
Depetris I, Marino D, Bonzano A, et al. Fluoropyrimidine-induced cardiotoxicity. Crit Rev Oncol Hematol 2018; 124: 1–10. https://doi.org/10.1016/j.critrevonc.2018.02.002
Yuan C, Parekh H, Allegra C, et al. 5-FU induced cardiotoxicity: case series and review of the literature. Cardio-Oncology 2019; 5: 13. https://doi.org/10.1186/s40959-019-0048-3
Chong JH, Ghosh AK. Coronary artery vasospasm induced by 5-fluorouracil: proposed mechanisms, existing management options and future directions. Interv Cardiol 2019; 14: 89–94. https://doi.org/10.15420/icr.2019.12
Peng J, Dong C, Wang C, et al. Cardiotoxicity of 5-fluorouracil and capecitabine in Chinese patients: a prospective study. Cancer Commun (Lond) 2018; 38: 22. https://doi.org/10.1186/s40880-018-0292-1
O’Brien PJ. Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity. Toxicology 2008; 245: 206–18. https://doi.org/10.1016/j.tox.2007.12.006
Dolci A, Dominici R, Cardinale D, et al. Biochemical markers for prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use. Am J Clin Pathol 2008; 130: 688–95. https://doi.org/10.1309/ajcpb66lriivmqdr
Abdel-Rahman O. 5-Fluorouracil-related cardiotoxicity; findings from five randomized studies of 5-fluorouracil-based regimens in metastatic colorectal cancer. Clin Colorectal Cancer; 18: 58–63. https://doi.org/10.1016/j.clcc.2018.10.006
Arshed S, Luo HX, Zafar S, et al. Elevated troponin I in the absence of coronary artery disease: a case report with review of literature. J Clin Med Res 2015; 7: 820–4. https://doi.org/10.14740/jocmr2280w
Saif MW, Quinn MG, Thomas RR, et al. Cardiac toxicity associated with capecitabine therapy. Acta Oncol 2003; 42: 342–4. https://doi.org/10.1080/02841860310011861
Cerny J, Hassan A, Smith C, Piperdi B. Coronary vasospasm with myocardial stunning in a patient with colon cancer receiving adjuvant chemotherapy with FOLFOX regimen. Clin Colorectal Cancer 2009; 8: 55–8. https://doi.org/10.3816/CCC.2009.n.009
More LA, Lane S, Asnani A. 5-FU cardiotoxicity: vasospasm, myocarditis, and sudden death. Curr Cardiol Rep 2021; 23: 17. https://doi.org/10.1007/s11886-021-01441-2
Jensen SA, Sørensen JB. 5-fluorouracil-based therapy induces endovascular injury having potential significance to development of clinically overt cardiotoxicity. Cancer Chemother Pharmacol 2012; 69: 57–64. https://doi.org/10.1007/s00280-011-1669-x
Feola M, Garrone O, Occelli M, et al. Cardiotoxicity after anthracycline chemotherapy in breast carcinoma: effects on left ventricular ejection fraction, troponin I and brain natriuretic peptide. Int J Cardiol 2011; 148: 194–8. https://doi.org/10.1016/j.ijcard.2009.09.564
Schöber C, Papageorgiou E, Harstrick A, et al. Cardiotoxicity of 5-fluorouracil in combination with folinic acid in patients with gastrointestinal cancer. Cancer 1993; 72: 2242–7. https://doi.org/10.1002/1097-0142 (19931001)72:7<2242::aid-cncr2820720730 >3.0.co;2-e
Aleksova A, Gagno G, Pierri A, et al. What the cardiologist needs to consider in the management of oncologic patients with STEMI-like syndrome: a case report and literature review. Pharmaceuticals 2021; 14: 563. https://doi.org/10.3390/ph14060563
Dyhl-Polk A, Schou M, Vistisen KK, et al. Myocardial ischemia induced by 5-fluorouracil: a prospective electrocardiographic and cardiac biomarker study. Oncologist 2021; 26: e403–13. https://doi.org/10.1002/onco.13536
Holubec L, Jr., Topolcan O, Finek J, et al. Dynamic monitoring of cardio-specific markers and markers of thyroid gland function in cancer patients — a pilot study. Anticancer Res 2007; 27: 1883–6.
Turan T, Agac MT, Aykan A, et al. Usefulness of heart-type fatty acid-binding protein and myocardial performance index for early detection of 5-fluorouracil cardiotoxicity. Angiology 2017; 68: 52–8. https://doi.org/10.1177/0003319716637516
Oztop I, Gencer M, Okan T, et al. Evaluation of cardiotoxicity of a combined bolus plus infusional 5-fluorouracil/folinic acid treatment by echocardiography, plasma troponin I level, QT interval and dispersion in patients with gastrointestinal system cancers. Jpn J Clin Oncol 2004; 34: 262–8. https://doi.org/10.1093/jjco/hyh047
Hollebecque A, Lanoy E, Troallen F, et al. Cardiac troponin I elevation and overall survival among cancer patients receiving investigational compounds during phase I trials. Int J Cardiol 2016; 214: 364–9. https://doi.org/10.1016/j.ijcard.2016.04.010
Sandoval Y, Sharain K, Saenger AK, et al. Clinical use of cardiac troponin for acute cardiac care and emerging opportunities in the outpatient setting. Minerva Med 2019; 110: 139–56. https://doi.org/10.23736/s0026-4806.18.05874-3
Sawaya H, Sebag IA, Plana JC, et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol 2011; 107: 1375–80. https://doi.org/10.1016/j.amjcard.2011.01.006
Layoun ME, Wickramasinghe CD, Peralta MV, Yang EH. Fluoropyrimidine-induced cardiotoxicity: manifestations, mechanisms, and management. Curr Oncol Rep 2016; 18: 35. https://doi.org/10.1007/s11912-016-0521-1
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