5-Fluorouracil, capecitabine and vasospasm: a scoping review of pathogenesis, management options and future research considerations

References

• Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330–338.
   PubMed Web of Science ®Google Scholar
• Siddiqui NS, Godara A, Byrne MM, et al. Capecitabine for the treatment of pancreatic cancer. Expert Opin Pharmacother. 2019;20(4):399–409.
   PubMed Web of Science ®Google Scholar
• Becker K, Erckenbrecht JF, Häussinger D, et al. Cardiotoxicity of the antiproliferative compound fluorouracil. Drugs. 1999;57(4):475–484.
   PubMed Web of Science ®Google Scholar
• Dyhl-Polk A, Vaage-Nilsen M, Schou M, et al. Incidence and risk markers of 5-fluorouracil and capecitabine cardiotoxicity in patients with colorectal cancer. Acta Oncol. 2020;59(4):475–483.
   PubMed Web of Science ®Google Scholar
• Anand AJ. Fluorouracil cardiotoxicity. Ann Pharmacother. 1994;28(3):374–378.
   PubMed Web of Science ®Google Scholar
• Forni M. d, Malet-Martino MC, Jaillais P, et al. Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J Clin Oncol. 1992;10(11):1795–1801.
   PubMed Web of Science ®Google Scholar
• 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(11):1542–1546.
   PubMed Web of Science ®Google Scholar
• Tsibiribi P, Descotes J, Lombard-Bohas C, et al. Cardiotoxicity of 5-fluorouracil in 1350 patients with no prior history of heart disease. Bull Cancer. 2006;93(3):E27–30.
   PubMedGoogle Scholar
• Wacker A, Lersch C, Scherpinski U, et al. High incidence of angina pectoris in patients treated with 5-fluorouracil. A planned surveillance study with 102 patients. Oncology. 2003;65(2):108–112.
   PubMed Web of Science ®Google Scholar
• Eskilsson J, Albertsson M, Mercke C. Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil. Radiother Oncol J Eur Soc Ther Radiol Oncol. 1988;13(1):41–46.
   PubMed Web of Science ®Google Scholar
• Kaise M, Yoshino M, Nagai H, et al. Risk factors for cardiotoxicity during fluorouracil and cisplatin combination chemotherapy. Gan to Kagaku Ryoho. 2014;41(5):601–604.
   PubMedGoogle Scholar
• Kwakman JJM, Simkens LHJ, Mol L, et al. Incidence of capecitabine-related cardiotoxicity in different treatment schedules of metastatic colorectal cancer: a retrospective analysis of the CAIRO studies of the Dutch Colorectal Cancer Group. Eur J Cancer. 2017;76:93–99.
   PubMed Web of Science ®Google Scholar
• Polk A, Shahmarvand N, Vistisen K, et al. Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity: a retrospective study of 452 consecutive patients with metastatic breast cancer. BMJ Open. 2016;6(10):e012798.
   PubMed Web of Science ®Google Scholar
• Koca D, Salman T, Unek IT, et al. Clinical and electrocardiography changes in patients treated with capecitabine. Chemotherapy. 2011;57(5):381–387.
   PubMed Web of Science ®Google Scholar
• Meyer CC, Calis KA, Burke LB, Walawander CA, et al. Symptomatic cardiotoxicity associated with 5-fluorouracil. Pharmacotherapy. 1997;17(4):729–736.
   PubMed Web of Science ®Google Scholar
• Labianca R, Beretta G, Clerici M, et al. Cardiac toxicity of 5-fluorouracil: a study on 1083 patients. Tumori. 1982;68(6):505–510.
   PubMed Web of Science ®Google Scholar
• Rezkalla S, Kloner RA, Ensley J, et al. Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study. J Clin Oncol. 1989;7(4):509–514.
   PubMed Web of Science ®Google Scholar
• Meydan N, Kundak I, Yavuzsen T, et al. Cardiotoxicity of de Gramont’s regimen: incidence, clinical characteristics and long-term follow-up. Jpn J Clin Oncol. 2005;35(5):265–270.
   PubMed Web of Science ®Google Scholar
• Jensen SA, Hasbak P, Mortensen J, et al. Fluorouracil induces myocardial ischemia with increases of plasma brain natriuretic peptide and lactic acid but without dysfunction of left ventricle. J Clin Oncol. 2010;28(36):5280–5286.
   PubMed Web of Science ®Google Scholar
• Khan MA, Masood N, Husain N, et al. A retrospective study of cardiotoxicities induced by 5-fluouracil (5-FU) and 5-FU based chemotherapy regimens in Pakistani adult cancer patients at Shaukat Khanum Memorial Cancer Hospital & Research Center. J Pak Med Assoc. 2012;62(5):430–434.
   PubMed Web of Science ®Google Scholar
• Canobbio L, Fassio T, Gasparini G, et al. Cardiac arrhythmia: possible complication from treatment with cisplatin. Tumori. 1986;72(2):201–204.
   PubMed Web of Science ®Google Scholar
• Fajardo LF, Stewart JR. Pathogenesis of radiation-induced myocardial fibrosis. Lab Invest. 1973;29(2):244–257.
   PubMed Web of Science ®Google Scholar
• Saif MW, Shah MM, Shah AR. Fluoropyrimidine-associated cardiotoxicity: revisited. Expert Opin Drug Saf. 2009;8(2):191–202.
   PubMed Web of Science ®Google Scholar
• Yilmaz U, Oztop I, Ciloglu A, et al. 5-fluorouracil increases the number and complexity of premature complexes in the heart: a prospective study using ambulatory ECG monitoring. Int J Clin Pract. 2007;61(5):795–801.
   PubMed Web of Science ®Google Scholar
• Grandi AM, Pinotti G, Morandi E, et al. Noninvasive evaluation of cardiotoxicity of 5-fluorouracil and low doses of folinic acid: a one-year follow-up study. Ann Oncol off J Eur Soc Med Oncol. 1997;8(7):705–708.
   PubMed Web of Science ®Google Scholar
• 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):974–984.
   PubMed Web of Science ®Google Scholar
• Yamagishi M, Miyatake K, Tamai J, et al. Intravascular ultrasound detection of atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed coronary segments. J Am Coll Cardiol. 1994;23(2):352–357.
   PubMed Web of Science ®Google Scholar
• Ceyhan C, Meydan N, Barutca S, et al. Ultrasound tissue characterization by integrated backscatter for analyzing Fluorouracil induced myocardial damage. Echocardiography. 2005;22(3):233–238.
   PubMed Web of Science ®Google Scholar
• 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(5):262–268.
   PubMed Web of Science ®Google Scholar
• Balloni L, Porta C, Rossi S, et al. Left ventricular function in colon cancer patients receiving adjuvant fluoro-folate chemotherapy: an echocardiographic study. Oncol Rep. 2000;7(4):887–890.
   PubMed Web of Science ®Google Scholar
• Katona C, Kralovánszky J, Rosta A, et al. Putative role of dihydropyrimidine dehydrogenase in the toxic side effect of 5-fluorouracil in colorectal cancer patients. Oncology. 1998;55(5):468–474.
   PubMed Web of Science ®Google Scholar
• Oshima T, Imada T, Nagashima Y, et al. Role of nitric oxide in human gastric cancer cells treated with 5-fluorouracil. Oncol Rep. 2001;8(4):847–849.
   PubMed Web of Science ®Google Scholar
• Gao Y, Zhou S, Xu Y, et al. Nitric oxide synthase inhibitors 1400W and L-NIO inhibit angiogenesis pathway of colorectal cancer. Nitric Oxide. 2019;83:33–39.
   PubMed Web of Science ®Google Scholar
• Jiang J, Liu J, Zhu J, et al. Mechanism of apoptotic effects induced by 5-fluorouracil on human liver carcinoma Bel7402 cell line. Chin Med J. 2002;115:968–971.
   PubMed Web of Science ®Google Scholar
• Islam S, Hassan F, Tumurkhuu G, et al. 5-Fluorouracil prevents lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells by inhibiting Akt-dependent nuclear factor-kappaB activation. Cancer Chemother Pharmacol. 2007;59(2):227–233.
   PubMed Web of Science ®Google Scholar
• Matthews NE, Adams MA, Maxwell LR, et al. Nitric oxide-mediated regulation of chemosensitivity in cancer cells. J Natl Cancer Inst. 2001;93(24):1879–1885.
   PubMedGoogle Scholar
• Jung ID, Yang SY, Park CG, et al. 5-Fluorouracil inhibits nitric oxide production through the inactivation of IkappaB kinase in stomach cancer cells. Biochem Pharmacol. 2002;64(10):1439–1445.
   PubMed Web of Science ®Google Scholar
• Jin Y, Heck DE, DeGeorge G, et al. 5-Fluorouracil suppresses nitric oxide biosynthesis in colon carcinoma cells. Cancer Res. 1996;56(9):1978–1982.
   PubMed Web of Science ®Google Scholar
• Leitão RFC, Ribeiro RA, Bellaguarda EAL, et al. Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster. Cancer Chemother Pharmacol. 2007;59(5):603–612.
   PubMed Web of Science ®Google Scholar
• Gajalakshmi P, Priya MK, Pradeep T, et al. Breast cancer drugs dampen vascular functions by interfering with nitric oxide signaling in endothelium. Toxicol Appl Pharmacol. 2013;269(2):121–131.
   PubMed Web of Science ®Google Scholar
• Sunpaweravong S, Puttawibul P, Ruangsin S, et al. Randomized study of antiinflammatory and immune-modulatory effects of enteral immunonutrition during concurrent chemoradiotherapy for esophageal cancer. Nutr Cancer. 2014;66(1):1–5.
   PubMed Web of Science ®Google Scholar
• Aquilani R, Brugnatelli S, Dossena M, et al. Oxaliplatin-fluoropyrimidine combination (XELOX) therapy does not affect plasma amino acid levels and plasma markers of oxidative stress in colorectal cancer surgery patients: a pilot study. Nutrients. 2019;11(11):2667.
   PubMed Web of Science ®Google Scholar
• Yin X-Y, Jiang J-M, Liu J-Y, et al. Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice. World J Gastroenterol. 2007;13(46):6249–6253.
   PubMed Web of Science ®Google Scholar
• Jahani M, Azadbakht M, Norooznezhad F, et al. l-arginine alters the effect of 5-fluorouracil on breast cancer cells in favor of apoptosis. Biomed Pharmacother. 2017;88:114–123.
   PubMed Web of Science ®Google Scholar
• Alsan Cetin I, Atasoy BM, Cilaker S, et al. A diet containing beta-hydroxy-beta-methylbutyrate, L-glutamine and L-arginine ameliorates chemoradiation-induced gastrointestinal injury in rats. Radiat Res. 2015;184(4):411–421.
   PubMed Web of Science ®Google Scholar
• Leocádio PCL, Antunes MM, Teixeira LG, et al. L-arginine pretreatment reduces intestinal mucositis as induced by 5-FU in mice. Nutr Cancer. 2015;67(3):486–493.
   PubMed Web of Science ®Google Scholar
• Badawoud MH, Elshal EB, Zaki AI, et al. The possible protective effect of L-arginine against 5-fluorouracil-induced nephrotoxicity in male albino rats. Folia Morphol. 2017;76(4):608–619.
   PubMed Web of Science ®Google Scholar
• Balmant BD, Araújo EON, Yabuki D, et al. Effects of L-arginine supplementation on leukogram, inflammatory bowel infiltrates and immunoglobulins with 5-FU use in rats. Nutr Cancer. 2018;70(2):249–256.
   PubMed Web of Science ®Google Scholar
• Andrade Bernal Fagiani M. d, Fluminhan A, Azevedo Mello F. d, et al. l-arginine minimizes immunosuppression and prothrombin time and enhances the genotoxicity of 5-fluorouracil in rats. Nutrition. 2019;66:94–100.
   PubMed Web of Science ®Google Scholar
• Jahani M, Azadbakht M, Rasouli H, et al. L-arginine/5-fluorouracil combination treatment approaches cells selectively: rescuing endothelial cells while killing MDA-MB-468 breast cancer cells. Food Chem Toxicol. 2019;123:399–411.
   PubMed Web of Science ®Google Scholar
• Lischke J, Lang C, Sawodny O, et al. Impairment of energy metabolism in cardiomyocytes caused by 5-FU catabolites can be compensated by administration of amino acids. Conf Proc. Annu Int Conf IEEE Eng Med Biol Soc IEEE Eng Med Biol Soc Annu Conf. 2015;2015:5363–5366.
   PubMedGoogle Scholar
• Alexandrou C, Al-Aqbi SS, Higgins JA, et al. Sensitivity of colorectal cancer to arginine deprivation therapy is shaped by differential expression of urea cycle enzymes. Sci Rep. 2018;8(1):12096.
   PubMed Web of Science ®Google Scholar
• Amraotkar AR, Pachika A, Grubb KJ, et al. Rapid extracorporeal membrane oxygenation overcomes fulminant myocarditis induced by 5-fluorouracil. Tex Heart Inst J. 2016;43(2):178–182.
   PubMed Web of Science ®Google Scholar
• Çalık AN, Çeliker E, Velibey Y, et al. Initial dose effect of 5-fluorouracil: rapidly improving severe, acute toxic myopericarditis. Am J Emerg Med. 2012;30(1):257.e1–257.e3.
   PubMed Web of Science ®Google Scholar
• Antonelli D, Beker B, Barzilay J. [Early cardiotoxicity of 5-fluorouracil]. G Ital Cardiol. 1981;11:1758–1761.
   PubMedGoogle Scholar
• Dent RG, McColl I. Letter: 5-fluorouracil and angina. Lancet. 1975;1:347–348.
   PubMed Web of Science ®Google Scholar
• MacMillan WE, Wolberg WH, Welling PG. Pharmacokinetics of fluorouracil in humans. Cancer Res. 1978;38(10):3479–3482.
   PubMed Web of Science ®Google Scholar
• Stevenson DL, Mikhailidis DP, Gillett DS. Cardiotoxicity of 5-fluorouracil. Lancet. 1977;2:406–407.
   PubMed Web of Science ®Google Scholar
• 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(7):2242–2247.
   PubMed Web of Science ®Google Scholar
• Freeman NJ, Costanza ME. 5-Fluorouracil-associated cardiotoxicity. Cancer. 1988;61(1):36–45.
   PubMed Web of Science ®Google Scholar
• Lenaz L, Page JA. Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat Rev. 1976;3(3):111–120.
   PubMed Web of Science ®Google Scholar
• Collins C, Weiden PL. Cardiotoxicity of 5-fluorouracil. Cancer Treat Rep. 1987;71(7–8):733–736.
   PubMedGoogle Scholar
• Anon. Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013). Circ J. 2014;78:2779–2801.
   PubMed Web of Science ®Google Scholar
• Patel B, Kloner RA, Ensley J, et al. 5-Fluorouracil cardiotoxicity: left ventricular dysfunction and effect of coronary vasodilators. Am J Med Sci. 1987;294(4):238–243.
   PubMed Web of Science ®Google Scholar
• Eskilsson J, Albertsson M. Failure of preventing 5-fluorouracil cardiotoxicity by prophylactic treatment with verapamil. Acta Oncol. 1990;29(8):1001–1003.
   PubMed Web of Science ®Google Scholar
• Nakae I, Matsumoto T, Horie H, et al. Effects of intravenous nicorandil on coronary circulation in humans: plasma concentration and action mechanism. J Cardiovasc Pharmacol. 2000;35:919–925.
   PubMed Web of Science ®Google Scholar
• Moriyama S, Yokoyama T, Irie K, et al. Atrial fibrillation observed in a patient with esophageal cancer treated with fluorouracil. J Cardiol Cases. 2019;20(5):183–186.
   PubMedGoogle Scholar
• Brun-Ly VL, Martin J, Venat-Bouvet L, et al. Cardiac toxicity with capecitabine, vinorelbine and trastuzumab therapy: case report and review of fluoropyrimidine-related cardiotoxicity. Oncology. 2009;76(5):322–325.
   PubMed Web of Science ®Google Scholar
• Nagumo H, Sasaki Y, Ono Y, et al. Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells. Am J Physiol Cell Physiol. 2000;278(1):C57–65.
   PubMed Web of Science ®Google Scholar
• Lestuzzi C, Crivellari D, Rigo F, et al. Capecitabine cardiac toxicity presenting as effort angina: a case report. J Cardiovasc Med. 2010;11:700–703.
   Google Scholar
• Cada DJ, Mbogu U, Bindler RJ, et al. Uridine triacetate. Hosp Pharm. 2016;51(6):484–488.
   PubMedGoogle Scholar
• Labianca R, Luporini G. 5-fluorouracil cardiotoxicity: the risk of rechallenge. Ann Oncol off J Eur Soc Med Oncol. 1991;2(5):383.
   PubMed Web of Science ®Google Scholar
• Kosmas C, Kallistratos MS, Kopterides P, et al. Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol. 2007;134(1):75–82.
   PubMed Web of Science ®Google Scholar
• Chakrabarti S, Sara J, Lobo R, et al. Bolus 5-fluorouracil (5-FU) In combination with oxaliplatin is safe and well tolerated in patients who experienced coronary vasospasm with Infusional 5-FU or Capecitabine. Clin Colorectal Cancer. 2019;18(1):52–57.
   PubMed Web of Science ®Google Scholar