{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:10:31Z","timestamp":1793139031446,"version":"4.5.0"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T00:00:00Z","timestamp":1584576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T00:00:00Z","timestamp":1584576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr. Treat. Options in Oncol."],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Opinion statement<\/jats:title><jats:p>Fluoropyrimidine (FP) is used to treat a wide range of cancers; however, it is associated with drug-induced vascular toxicity, as well as angina pectoris and coronary spasm. FP has been administered for many years, although the incidence, mechanisms, and appropriate methods for managing its associated cardiovascular toxicities have not been clarified, and the management of these complications has not been standardized. This lack of evidence is not limited to FP. Many trials of anticancer agents have been conducted, excluding patients with heart diseases. Hence, there is a paucity of epidemiological data on cardiovascular adverse events caused by anticancer agents. There have been remarkable improvements in cancer treatment in recent years, with consequent improvements in prognosis. In this context, new cardiovascular toxicities related to new drugs have emerged. We are now compelled to respond to cardiovascular adverse events despite the lack of evidence regarding optimal management. The result has been establishment and rapid maturation of the new academic field of cardio-oncology. Despite the relative lack of evidence, we must review small pieces of evidence that have accumulated to date and make the utmost efforts to provide patients with effective evidence-based medical care. Simultaneously, we urgently need randomized clinical trials to build strong evidence.<\/jats:p>","DOI":"10.1007\/s11864-020-0719-1","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T07:02:57Z","timestamp":1586242977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Cardiotoxicities of 5-Fluorouracil and Other Fluoropyrimidines"],"prefix":"10.1007","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4205-7534","authenticated-orcid":false,"given":"Taro","family":"Shiga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Hiraide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,19]]},"reference":[{"key":"719_CR1","unstructured":"Cancer incidence and mortality worldwide: IARC CancerBase. http:\/\/gco.iarc.fr\/tomorrow\/home. Accessed 9 Dec 2019."},{"issue":"25","key":"719_CR2","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1016\/j.jacc.2015.04.059","volume":"65","author":"A Barac","year":"2015","unstructured":"Barac A, Murtagh G, Carver JR, Chen MH, Freeman AM, Herrmann J, et al. Cardiovascular health of patients with cancer and cancer survivors: a roadmap to the next level. J Am Coll Cardiol. 2015;65(25):2739\u201346. https:\/\/doi.org\/10.1016\/j.jacc.2015.04.059.","journal-title":"J Am Coll Cardiol"},{"issue":"6","key":"719_CR3","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1161\/CIRCRESAHA.115.303633","volume":"118","author":"CG Lenneman","year":"2016","unstructured":"Lenneman CG, Sawyer DB. Cardio-oncology: an update on cardiotoxicity of cancer-related treatment. Circ Res. 2016;118(6):1008\u201320. https:\/\/doi.org\/10.1161\/CIRCRESAHA.115.303633.","journal-title":"Circ Res"},{"issue":"10","key":"719_CR4","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1200\/JCO.1988.6.10.1653","volume":"6","author":"HM Pinedo","year":"1988","unstructured":"Pinedo HM, Peters GF. Fluorouracil: biochemistry and pharmacology. J Clin Oncol. 1988;6(10):1653\u201364. https:\/\/doi.org\/10.1200\/JCO.1988.6.10.1653.","journal-title":"J Clin Oncol"},{"issue":"3","key":"719_CR5","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1046\/j.1365-2125.1999.00010.x","volume":"48","author":"AA Adjei","year":"1999","unstructured":"Adjei AA. A review of the pharmacology and clinical activity of new chemotherapy agents for the treatment of colorectal cancer. Br J Clin Pharmacol. 1999;48(3):265\u201377. https:\/\/doi.org\/10.1046\/j.1365-2125.1999.00010.x.","journal-title":"Br J Clin Pharmacol"},{"issue":"8","key":"719_CR6","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/j.ctrv.2013.03.005","volume":"39","author":"A Polk","year":"2013","unstructured":"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\u201384. https:\/\/doi.org\/10.1016\/j.ctrv.2013.03.005.","journal-title":"Cancer Treat Rev"},{"issue":"1","key":"719_CR7","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00280-011-1669-x","volume":"69","author":"SA Jensen","year":"2012","unstructured":"Jensen SA, Sorensen JB. 5-fluorouracil-based therapy induces endovascular injury having potential significance to development of clinically overt cardiotoxicity. Cancer Chemother Pharmacol. 2012;69(1):57\u201364. https:\/\/doi.org\/10.1007\/s00280-011-1669-x.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"2","key":"719_CR8","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1517\/14740330902733961","volume":"8","author":"MW Saif","year":"2009","unstructured":"Saif MW, Shah MM, Shah AR. Fluoropyrimidine-associated cardiotoxicity: revisited. Expert Opin Drug Saf. 2009;8(2):191\u2013202. https:\/\/doi.org\/10.1517\/14740330902733961.","journal-title":"Expert Opin Drug Saf"},{"issue":"4","key":"719_CR9","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1111\/j.1445-5994.2009.02144.x","volume":"40","author":"T Stewart","year":"2010","unstructured":"Stewart T, Pavlakis N, Ward M. Cardiotoxicity with 5-fluorouracil and capecitabine: more than just vasospastic angina. Intern Med J. 2010;40(4):303\u20137. https:\/\/doi.org\/10.1111\/j.1445-5994.2009.02144.x.","journal-title":"Intern Med J"},{"issue":"5","key":"719_CR10","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/annonc\/mdu055","volume":"25","author":"C Lestuzzi","year":"2014","unstructured":"Lestuzzi C, Vaccher E, Talamini R, Lleshi A, Meneguzzo N, Viel E, et al. Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk. Ann Oncol. 2014;25(5):1059\u201364. https:\/\/doi.org\/10.1093\/annonc\/mdu055.","journal-title":"Ann Oncol"},{"issue":"11","key":"719_CR11","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1200\/JCO.1992.10.11.1795","volume":"10","author":"M de Forni","year":"1992","unstructured":"de Forni M, Malet-Martino MC, Jaillais P, Shubinski RE, Bachaud JM, Lemaire L, et al. Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J Clin Oncol. 1992;10(11):1795\u2013801. https:\/\/doi.org\/10.1200\/JCO.1992.10.11.1795.","journal-title":"J Clin Oncol"},{"issue":"2","key":"719_CR12","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1159\/000072334","volume":"65","author":"A Wacker","year":"2003","unstructured":"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\u201312. https:\/\/doi.org\/10.1159\/000072334.","journal-title":"Oncology."},{"issue":"1","key":"719_CR13","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00432-007-0250-9","volume":"134","author":"C Kosmas","year":"2008","unstructured":"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\u201382. https:\/\/doi.org\/10.1007\/s00432-007-0250-9.","journal-title":"J Cancer Res Clin Oncol"},{"issue":"2","key":"719_CR14","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1002\/1097-0142(19930115)71:2<493::aid-cncr2820710235>3.0.co;2-c","volume":"71","author":"NC Robben","year":"1993","unstructured":"Robben NC, Pippas AW, Moore JO. The syndrome of 5-fluorouracil cardiotoxicity. An elusive cardiopathy. Cancer. 1993;71(2):493\u2013509. https:\/\/doi.org\/10.1002\/1097-0142(19930115)71:2<493::aid-cncr2820710235>3.0.co;2-c.","journal-title":"Cancer."},{"issue":"11","key":"719_CR15","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1002\/j.1552-4604.1993.tb01943.x","volume":"33","author":"DL Keefe","year":"1993","unstructured":"Keefe DL, Roistacher N, Pierri MK. Clinical cardiotoxicity of 5-fluorouracil. J Clin Pharmacol. 1993;33(11):1060\u201370. https:\/\/doi.org\/10.1002\/j.1552-4604.1993.tb01943.x.","journal-title":"J Clin Pharmacol"},{"issue":"7","key":"719_CR16","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1002\/1097-0142(19931001)72:7<2242::aid-cncr2820720730>3.0.co;2-e","volume":"72","author":"C Schober","year":"1993","unstructured":"Schober C, Papageorgiou E, Harstrick A, Bokemeyer C, Mugge A, Stahl M, et al. Cardiotoxicity of 5-fluorouracil in combination with folinic acid in patients with gastrointestinal cancer. Cancer. 1993;72(7):2242\u20137. https:\/\/doi.org\/10.1002\/1097-0142(19931001)72:7<2242::aid-cncr2820720730>3.0.co;2-e.","journal-title":"Cancer."},{"issue":"4","key":"719_CR17","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1080\/1120009x.1990.11739029","volume":"2","author":"B Jeremic","year":"1990","unstructured":"Jeremic B, Jevremovic S, Djuric L, Mijatovic L. Cardiotoxicity during chemotherapy treatment with 5-fluorouracil and cisplatin. J Chemother. 1990;2(4):264\u20137. https:\/\/doi.org\/10.1080\/1120009x.1990.11739029.","journal-title":"J Chemother"},{"issue":"85","key":"719_CR18","first-page":"1249","volume":"55","author":"N Manojlovic","year":"2008","unstructured":"Manojlovic N, Babic D, Stojanovic S, Filipovic I, Radoje D. Capecitabine cardiotoxicity--case reports and literature review. Hepatogastroenterology. 2008;55(85):1249\u201356.","journal-title":"Hepatogastroenterology."},{"issue":"3","key":"719_CR19","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s00280-019-03888-1","volume":"84","author":"X Jin","year":"2019","unstructured":"Jin X, Bai Y, Gao L, Wu S. Incidence of and risk factors for cardiotoxicity after fluorouracil-based chemotherapy in locally advanced or metastatic gastric cancer patients. Cancer Chemother Pharmacol. 2019;84(3):599\u2013607. https:\/\/doi.org\/10.1007\/s00280-019-03888-1.","journal-title":"Cancer Chemother Pharmacol"},{"key":"719_CR20","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ejca.2017.02.009","volume":"76","author":"JJ Kwakman","year":"2017","unstructured":"Kwakman JJ, Simkens LH, Mol L, Kok WE, Koopman M, Punt CJ. 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\u20139. https:\/\/doi.org\/10.1016\/j.ejca.2017.02.009.","journal-title":"Eur J Cancer"},{"issue":"1","key":"719_CR21","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1177\/0003319716637516","volume":"68","author":"T Turan","year":"2017","unstructured":"Turan T, Agac MT, Aykan AC, Kul S, Akyuz AR, Gokdeniz T, et al. Usefulness of heart-type fatty acid-binding protein and myocardial performance index for early detection of 5-fluorouracil cardiotoxicity. Angiology. 2017;68(1):52\u20138. https:\/\/doi.org\/10.1177\/0003319716637516.","journal-title":"Angiology."},{"issue":"2","key":"719_CR22","doi-asserted-by":"publisher","first-page":"150","DOI":"10.5603\/KP.a2016.0163","volume":"75","author":"E Plonska-Gosciniak","year":"2017","unstructured":"Plonska-Gosciniak E, Rozewicz M, Kasprzak J, Wojtarowicz A, Mizia-Stec K, Hryniewiecki T, 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\u20136. https:\/\/doi.org\/10.5603\/KP.a2016.0163.","journal-title":"Kardiol Pol"},{"issue":"10","key":"719_CR23","doi-asserted-by":"publisher","first-page":"e012798","DOI":"10.1136\/bmjopen-2016-012798","volume":"6","author":"A Polk","year":"2016","unstructured":"Polk A, Shahmarvand N, Vistisen K, Vaage-Nilsen M, Larsen FO, Schou M, 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. https:\/\/doi.org\/10.1136\/bmjopen-2016-012798.","journal-title":"BMJ Open"},{"issue":"5","key":"719_CR24","first-page":"430","volume":"62","author":"MA Khan","year":"2012","unstructured":"Khan MA, Masood N, Husain N, Ahmad B, Aziz T, Naeem A. 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\u20134.","journal-title":"J Pak Med Assoc"},{"issue":"5","key":"719_CR25","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1159\/000331645","volume":"57","author":"D Koca","year":"2011","unstructured":"Koca D, Salman T, Unek IT, Oztop I, Ellidokuz H, Eren M, et al. Clinical and electrocardiography changes in patients treated with capecitabine. Chemotherapy. 2011;57(5):381\u20137. https:\/\/doi.org\/10.1159\/000331645.","journal-title":"Chemotherapy."},{"issue":"2","key":"719_CR26","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1007\/s12032-009-9226-8","volume":"27","author":"T Salepci","year":"2010","unstructured":"Salepci T, Seker M, Uyarel H, Gumus M, Bilici A, Ustaalioglu BB, et al. 5-Fluorouracil induces arterial vasoconstrictions but does not increase angiotensin II levels. Med Oncol. 2010;27(2):416\u201320. https:\/\/doi.org\/10.1007\/s12032-009-9226-8.","journal-title":"Med Oncol"},{"issue":"5","key":"719_CR27","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1111\/j.1742-1241.2007.01323.x","volume":"61","author":"U Yilmaz","year":"2007","unstructured":"Yilmaz U, Oztop I, Ciloglu A, Okan T, Tekin U, Yaren 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\u2013801. https:\/\/doi.org\/10.1111\/j.1742-1241.2007.01323.x.","journal-title":"Int J Clin Pract"},{"issue":"4A","key":"719_CR28","first-page":"1883","volume":"27","author":"L Holubec Jr","year":"2007","unstructured":"Holubec L Jr, Topolcan O, Finek J, Salvet J, Svoboda T, Svobodova S, et al. Dynamic monitoring of cardio-specific markers and markers of thyroid gland function in cancer patients--a pilot study. Anticancer Res. 2007;27(4A):1883\u20136.","journal-title":"Anticancer Res"},{"issue":"3","key":"719_CR29","first-page":"E27","volume":"93","author":"P Tsibiribi","year":"2006","unstructured":"Tsibiribi P, Descotes J, Lombard-Bohas C, Barel C, Bui-Xuan B, Belkhiria M, et al. Cardiotoxicity of 5-fluorouracil in 1350 patients with no prior history of heart disease. Bull Cancer. 2006;93(3):E27\u201330.","journal-title":"Bull Cancer"},{"issue":"4","key":"719_CR30","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/s00280-005-0178-1","volume":"58","author":"SA Jensen","year":"2006","unstructured":"Jensen SA, Sorensen JB. Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine. Cancer Chemother Pharmacol. 2006;58(4):487\u201393. https:\/\/doi.org\/10.1007\/s00280-005-0178-1.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"2","key":"719_CR31","first-page":"205","volume":"10","author":"N Tsavaris","year":"2005","unstructured":"Tsavaris N, Kosmas C, Vadiaka M, Skopelitis E, Kopteridis P, Pamouki S, et al. 5-fluorouracil cardiotoxicity is a rare, dose and schedule-dependent adverse event: a prospective study. J BUON. 2005;10(2):205\u201311.","journal-title":"J BUON"},{"issue":"3","key":"719_CR32","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/j.0742-2822.2005.03169.x","volume":"22","author":"C Ceyhan","year":"2005","unstructured":"Ceyhan C, Meydan N, Barutca S, Tekten T, Onbasili AO, Ozturk B, et al. Ultrasound tissue characterization by integrated backscatter for analyzing fluorouracil induced myocardial damage. Echocardiography. 2005;22(3):233\u20138. https:\/\/doi.org\/10.1111\/j.0742-2822.2005.03169.x.","journal-title":"Echocardiography."},{"issue":"11","key":"719_CR33","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1016\/j.ejca.2005.03.027","volume":"41","author":"M Ng","year":"2005","unstructured":"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\u20136. https:\/\/doi.org\/10.1016\/j.ejca.2005.03.027.","journal-title":"Eur J Cancer"},{"issue":"5","key":"719_CR34","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1093\/jjco\/hyi071","volume":"35","author":"N Meydan","year":"2005","unstructured":"Meydan N, Kundak I, Yavuzsen T, Oztop I, Barutca S, Yilmaz U, et al. Cardiotoxicity of de Gramont\u2019s regimen: incidence, clinical characteristics and long-term follow-up. Jpn J Clin Oncol. 2005;35(5):265\u201370. https:\/\/doi.org\/10.1093\/jjco\/hyi071.","journal-title":"Jpn J Clin Oncol"},{"issue":"3","key":"719_CR35","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1159\/000077884","volume":"50","author":"S Barutca","year":"2004","unstructured":"Barutca S, Ceyhan C, Meydan N, Ozturk B, Tekten T, Onbasili A, et al. A new perspective on cardiotoxicity of 5-fluorouracil. A novel research tool \u2018cardiac ultrasonic integrated backscatter analysis\u2019 indicates transient, subclinical myocardial dysfunction due to high-dose leucovorin and infusional 5-fluorouracil regimen. Chemotherapy. 2004;50(3):113\u20138. https:\/\/doi.org\/10.1159\/000077884.","journal-title":"Chemotherapy."},{"issue":"5","key":"719_CR36","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1093\/jjco\/hyh047","volume":"34","author":"I Oztop","year":"2004","unstructured":"Oztop I, Gencer M, Okan T, Yaren A, Altekin E, Turker S, 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\u20138. https:\/\/doi.org\/10.1093\/jjco\/hyh047.","journal-title":"Jpn J Clin Oncol"},{"issue":"4","key":"719_CR37","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1093\/annonc\/mdh150","volume":"15","author":"T Sudhoff","year":"2004","unstructured":"Sudhoff T, Enderle MD, Pahlke M, Petz C, Teschendorf C, Graeven U, et al. 5-Fluorouracil induces arterial vasocontractions. Ann Oncol. 2004;15(4):661\u20134. https:\/\/doi.org\/10.1093\/annonc\/mdh150.","journal-title":"Ann Oncol"},{"issue":"3","key":"719_CR38","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1093\/annonc\/mdf108","volume":"13","author":"E Van Cutsem","year":"2002","unstructured":"Van Cutsem E, Hoff PM, Blum JL, Abt M, Osterwalder B. Incidence of cardiotoxicity with the oral fluoropyrimidine capecitabine is typical of that reported with 5-fluorouracil. Ann Oncol. 2002;13(3):484\u20135. https:\/\/doi.org\/10.1093\/annonc\/mdf108.","journal-title":"Ann Oncol"},{"issue":"4","key":"719_CR39","doi-asserted-by":"publisher","first-page":"887","DOI":"10.3892\/or.7.4.887","volume":"7","author":"L Balloni","year":"2000","unstructured":"Balloni L, Porta C, Rossi S, Gola A, Pugliese P, Ferrari S, et al. Left ventricular function in colon cancer patients receiving adjuvant fluoro-folate chemotherapy: an echocardiographic study. Oncol Rep. 2000;7(4):887\u201390. https:\/\/doi.org\/10.3892\/or.7.4.887.","journal-title":"Oncol Rep"},{"issue":"6","key":"719_CR40","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1177\/030089168206800609","volume":"68","author":"R Labianca","year":"1982","unstructured":"Labianca R, Beretta G, Clerici M, Fraschini P, Luporini G. Cardiac toxicity of 5-fluorouracil: a study on 1083 patients. Tumori. 1982;68(6):505\u201310.","journal-title":"Tumori."},{"issue":"4","key":"719_CR41","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1002\/j.1875-9114.1997.tb03748.x","volume":"17","author":"CC Meyer","year":"1997","unstructured":"Meyer CC, Calis KA, Burke LB, Walawander CA, Grasela TH. Symptomatic cardiotoxicity associated with 5-fluorouracil. Pharmacotherapy. 1997;17(4):729\u201336. https:\/\/doi.org\/10.1002\/j.1875-9114.1997.tb03748.x.","journal-title":"Pharmacotherapy."},{"issue":"Suppl 5","key":"719_CR42","doi-asserted-by":"publisher","first-page":"v277","DOI":"10.1093\/annonc\/mdq200","volume":"21","author":"D Bovelli","year":"2010","unstructured":"Bovelli D, Plataniotis G, Roila F, Group EGW. Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. Ann Oncol. 2010;21(Suppl 5):v277\u201382. https:\/\/doi.org\/10.1093\/annonc\/mdq200.","journal-title":"Ann Oncol"},{"issue":"4","key":"719_CR43","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1200\/JCO.1989.7.4.509","volume":"7","author":"S Rezkalla","year":"1989","unstructured":"Rezkalla S, Kloner RA, Ensley J, al Sarraf M, Revels S, Olivenstein A, et al. Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study. J Clin Oncol. 1989;7(4):509\u201314. https:\/\/doi.org\/10.1200\/JCO.1989.7.4.509.","journal-title":"J Clin Oncol"},{"issue":"5","key":"719_CR44","doi-asserted-by":"publisher","first-page":"453","DOI":"10.5603\/cj.2012.0084","volume":"19","author":"MF Sorrentino","year":"2012","unstructured":"Sorrentino MF, Kim J, Foderaro AE, Truesdell AG. 5-fluorouracil induced cardiotoxicity: review of the literature. Cardiol J. 2012;19(5):453\u20138. https:\/\/doi.org\/10.5603\/cj.2012.0084.","journal-title":"Cardiol J"},{"issue":"3","key":"719_CR45","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1177\/106002809402800314","volume":"28","author":"AJ Anand","year":"1994","unstructured":"Anand AJ. Fluorouracil cardiotoxicity. Ann Pharmacother. 1994;28(3):374\u20138. https:\/\/doi.org\/10.1177\/106002809402800314.","journal-title":"Ann Pharmacother"},{"key":"719_CR46","doi-asserted-by":"publisher","first-page":"175883591878014","DOI":"10.1177\/1758835918780140","volume":"10","author":"JD Sara","year":"2018","unstructured":"Sara JD, Kaur J, Khodadadi R, Rehman M, Lobo R, Chakrabarti S, et al. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol. 2018;10:1758835918780140. https:\/\/doi.org\/10.1177\/1758835918780140.","journal-title":"Ther Adv Med Oncol"},{"issue":"36","key":"719_CR47","doi-asserted-by":"publisher","first-page":"5280","DOI":"10.1200\/JCO.2009.27.3953","volume":"28","author":"SA Jensen","year":"2010","unstructured":"Jensen SA, Hasbak P, Mortensen J, Sorensen JB. 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\u20136. https:\/\/doi.org\/10.1200\/JCO.2009.27.3953.","journal-title":"J Clin Oncol"},{"issue":"1","key":"719_CR48","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.clcc.2018.08.001","volume":"18","author":"JN Upshaw","year":"2019","unstructured":"Upshaw JN, O'Neill A, Carver JR, Dimond EP, Denlinger CS, Kircher SM, et al. Fluoropyrimidine cardiotoxicity: time for a contemporaneous appraisal. Clin Colorectal Cancer. 2019;18(1):44\u201351. https:\/\/doi.org\/10.1016\/j.clcc.2018.08.001.","journal-title":"Clin Colorectal Cancer"},{"issue":"8","key":"719_CR49","doi-asserted-by":"publisher","first-page":"637","DOI":"10.2459\/01.JCM.0000237914.12915.dd","volume":"7","author":"E Hrovatin","year":"2006","unstructured":"Hrovatin E, Viel E, Lestuzzi C, Tartuferi L, Zardo F, Brieda M, et al. Severe ventricular dysrhythmias and silent ischemia during infusion of the antimetabolite 5-fluorouracil and cis-platin. J Cardiovasc Med (Hagerstown). 2006;7(8):637\u201340. https:\/\/doi.org\/10.2459\/01.JCM.0000237914.12915.dd.","journal-title":"J Cardiovasc Med (Hagerstown)"},{"issue":"3","key":"719_CR50","doi-asserted-by":"publisher","first-page":"169","DOI":"10.4103\/0973-1482.37412","volume":"3","author":"K Talapatra","year":"2007","unstructured":"Talapatra K, Rajesh I, Rajesh B, Selvamani B, Subhashini J. Transient asymptomatic bradycardia in patients on infusional 5-fluorouracil. J Cancer Res Ther. 2007;3(3):169\u201371. https:\/\/doi.org\/10.4103\/0973-1482.37412.","journal-title":"J Cancer Res Ther"},{"issue":"3","key":"719_CR51","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.clcc.2015.02.005","volume":"14","author":"S Lai","year":"2015","unstructured":"Lai S, Marshall JL, Morrissey RL. Rechallenging 5-fluorouracil in a patient with capecitabine-induced ventricular fibrillation. Clin Colorectal Cancer. 2015;14(3):198\u2013201. https:\/\/doi.org\/10.1016\/j.clcc.2015.02.005.","journal-title":"Clin Colorectal Cancer"},{"key":"719_CR52","doi-asserted-by":"publisher","first-page":"206765","DOI":"10.1155\/2013\/206765","volume":"2013","author":"SH Lim","year":"2013","unstructured":"Lim SH, Wilson SM, Hunter A, Hill J, Beale P. Takotsubo cardiomyopathy and 5-fluorouracil: getting to the heart of the matter. Case Rep Oncol Med. 2013;2013:206765. https:\/\/doi.org\/10.1155\/2013\/206765.","journal-title":"Case Rep Oncol Med"},{"issue":"4","key":"719_CR53","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1097\/MBC.0b013e328329e431","volume":"20","author":"M Gianni","year":"2009","unstructured":"Gianni M, Dentali F, Lonn E. 5 flourouracil-induced apical ballooning syndrome: a case report. Blood Coagul Fibrinolysis. 2009;20(4):306\u20138. https:\/\/doi.org\/10.1097\/MBC.0b013e328329e431.","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"1","key":"719_CR54","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.clcc.2018.09.006","volume":"18","author":"S Chakrabarti","year":"2019","unstructured":"Chakrabarti S, Sara J, Lobo R, Eiring R, Finnes H, Mitchell J, 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\u20137. https:\/\/doi.org\/10.1016\/j.clcc.2018.09.006.","journal-title":"Clin Colorectal Cancer"},{"key":"719_CR55","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.2147\/OTT.S65653","volume":"7","author":"C Fontanella","year":"2014","unstructured":"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\u201391. https:\/\/doi.org\/10.2147\/OTT.S65653.","journal-title":"Onco Targets Ther"},{"issue":"5","key":"719_CR56","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.jccase.2019.08.005","volume":"20","author":"S Moriyama","year":"2019","unstructured":"Moriyama S, Yokoyama T, Irie K, Ito M, Tsuchihashi K, Fukata M, et al. Atrial fibrillation observed in a patient with esophageal cancer treated with fluorouracil. J Cardiol Cases. 2019;20(5):183\u20136. https:\/\/doi.org\/10.1016\/j.jccase.2019.08.005.","journal-title":"J Cardiol Cases"},{"issue":"3\u20134","key":"719_CR57","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s12029-009-9101-z","volume":"40","author":"CE Paiva","year":"2009","unstructured":"Paiva CE, Paiva BS, Garita R, Michelin OC, Okoshi K. Acute coronary syndrome associated with continuous 5-fluorouracil infusion in a patient with metastatic colorectal cancer-a case report with a discussion on this clinical dilemma. J Gastrointest Cancer. 2009;40(3\u20134):133\u20137. https:\/\/doi.org\/10.1007\/s12029-009-9101-z.","journal-title":"J Gastrointest Cancer"},{"issue":"9","key":"719_CR58","doi-asserted-by":"publisher","first-page":"722","DOI":"10.2459\/JCM.0b013e32832bb9b1","volume":"10","author":"A Farina","year":"2009","unstructured":"Farina A, Malafronte C, Valsecchi MA, Achilli F. Capecitabine-induced cardiotoxicity: when to suspect? How to manage? A case report. J Cardiovasc Med (Hagerstown). 2009;10(9):722\u20136. https:\/\/doi.org\/10.2459\/JCM.0b013e32832bb9b1.","journal-title":"J Cardiovasc Med (Hagerstown)"},{"key":"719_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.critrevonc.2018.02.002","volume":"124","author":"I Depetris","year":"2018","unstructured":"\u2022\u2022 Depetris I, Marino D, Bonzano A, Cagnazzo C, Filippi R, Aglietta M, et al. Fluoropyrimidine-induced cardiotoxicity. Crit Rev Oncol Hematol. 2018;124:1\u201310. https:\/\/doi.org\/10.1016\/j.critrevonc.2018.02.002 The accumulation of toxic metabolites produced by 5-FU catabolism may lead to cardiotoxicity.","journal-title":"Crit Rev Oncol Hematol"},{"key":"719_CR60","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/2050-6511-15-47","volume":"15","author":"A Polk","year":"2014","unstructured":"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.","journal-title":"BMC Pharmacol Toxicol"},{"issue":"36","key":"719_CR61","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1093\/eurheartj\/ehw211","volume":"37","author":"JL Zamorano","year":"2016","unstructured":"\u2022\u2022 Zamorano JL, Lancellotti P, Rodriguez Munoz D, Aboyans V, Asteggiano R, Galderisi M, et al. 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):2768\u2013801. https:\/\/doi.org\/10.1093\/eurheartj\/ehw211 Position paper about cardio-oncology written under the auspices of the ESC Committee for Practice Guidelines.","journal-title":"Eur Heart J"},{"issue":"3\u20134","key":"719_CR62","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/sj.bjc.6690098","volume":"79","author":"G Milano","year":"1999","unstructured":"Milano G, Etienne MC, Pierrefite V, Barberi-Heyob M, Deporte-Fety R, Renee N. Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br J Cancer. 1999;79(3\u20134):627\u201330. https:\/\/doi.org\/10.1038\/sj.bjc.6690098.","journal-title":"Br J Cancer"},{"issue":"4","key":"719_CR63","doi-asserted-by":"publisher","first-page":"231","DOI":"10.3816\/CCC.2009.n.039","volume":"8","author":"A Shahrokni","year":"2009","unstructured":"Shahrokni A, Rajebi MR, Saif MW. Toxicity and efficacy of 5-fluorouracil and capecitabine in a patient with TYMS gene polymorphism: a challenge or a dilemma? Clin Colorectal Cancer. 2009;8(4):231\u20134. https:\/\/doi.org\/10.3816\/CCC.2009.n.039.","journal-title":"Clin Colorectal Cancer"},{"issue":"4","key":"719_CR64","first-page":"531","volume":"27","author":"MW Saif","year":"2013","unstructured":"Saif MW, Garcon MC, Rodriguez G, Rodriguez T. Bolus 5-fluorouracil as an alternative in patients with cardiotoxicity associated with infusion 5-fluorouracil and capecitabine: a case series. In Vivo. 2013;27(4):531\u20134.","journal-title":"In Vivo"},{"issue":"10","key":"719_CR65","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1016\/0277-5379(88)90062-4","volume":"24","author":"A Thyss","year":"1988","unstructured":"Thyss A, Milano G, Schneider M, Demard F. Circulating drug levels in patients presenting cardiotoxicity to 5-FU. Eur J Cancer Clin Oncol. 1988;24(10):1675\u20136. https:\/\/doi.org\/10.1016\/0277-5379(88)90062-4.","journal-title":"Eur J Cancer Clin Oncol"},{"issue":"6","key":"719_CR66","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s10147-005-0516-7","volume":"10","author":"K Muneoka","year":"2005","unstructured":"Muneoka K, Shirai Y, Yokoyama N, Wakai T, Hatakeyama K. 5-Fluorouracil cardiotoxicity induced by alpha-fluoro-beta-alanine. Int J Clin Oncol. 2005;10(6):441\u20133. https:\/\/doi.org\/10.1007\/s10147-005-0516-7.","journal-title":"Int J Clin Oncol"},{"issue":"2","key":"719_CR67","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/jat.1118","volume":"26","author":"NV Goncharov","year":"2006","unstructured":"Goncharov NV, Jenkins RO, Radilov AS. Toxicology of fluoroacetate: a review, with possible directions for therapy research. J Appl Toxicol. 2006;26(2):148\u201361. https:\/\/doi.org\/10.1002\/jat.1118.","journal-title":"J Appl Toxicol"},{"issue":"3","key":"719_CR68","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1249\/01.mss.0000117130.91142.38","volume":"36","author":"R Hayward","year":"2004","unstructured":"Hayward R, Ruangthai R, Schneider CM, Hyslop RM, Strange R, Westerlind KC. Training enhances vascular relaxation after chemotherapy-induced vasoconstriction. Med Sci Sports Exerc. 2004;36(3):428\u201334. https:\/\/doi.org\/10.1249\/01.mss.0000117130.91142.38.","journal-title":"Med Sci Sports Exerc"},{"issue":"2","key":"719_CR69","first-page":"561","volume":"9","author":"M Cwikiel","year":"1995","unstructured":"Cwikiel M, Zhang B, Eskilsson J, Wieslander JB, Albertsson M. The influence of 5-fluorouracil on the endothelium in small arteries. An electron microscopic study in rabbits. Scanning Microsc. 1995;9(2):561\u201376.","journal-title":"Scanning Microsc"},{"issue":"1","key":"719_CR70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/sca.4950230101","volume":"23","author":"S Kinhult","year":"2001","unstructured":"Kinhult S, Albertsson M, Eskilsson J, Cwikiel M. Antithrombotic treatment in protection against thrombogenic effects of 5-fluorouracil on vascular endothelium: a scanning microscopy evaluation. Scanning. 2001;23(1):1\u20138. https:\/\/doi.org\/10.1002\/sca.4950230101.","journal-title":"Scanning."},{"issue":"1","key":"719_CR71","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1093\/oxfordjournals.annonc.a058084","volume":"3","author":"A Thyss","year":"1992","unstructured":"Thyss A, Gaspard MH, Marsault R, Milano G, Frelin C, Schneider M. Very high endothelin plasma levels in patients with 5-FU cardiotoxicity. Ann Oncol. 1992;3(1):88. https:\/\/doi.org\/10.1093\/oxfordjournals.annonc.a058084.","journal-title":"Ann Oncol"},{"issue":"13","key":"719_CR72","first-page":"3028","volume":"53","author":"M Mosseri","year":"1993","unstructured":"Mosseri M, Fingert HJ, Varticovski L, Chokshi S, Isner JM. 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(13):3028\u201333.","journal-title":"Cancer Res"},{"issue":"2","key":"719_CR73","doi-asserted-by":"publisher","first-page":"e0115686","DOI":"10.1371\/journal.pone.0115686","volume":"10","author":"C Focaccetti","year":"2015","unstructured":"Focaccetti C, Bruno A, Magnani E, Bartolini D, Principi E, Dallaglio K, et al. Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes. PLoS One. 2015;10(2):e0115686. https:\/\/doi.org\/10.1371\/journal.pone.0115686.","journal-title":"PLoS One"},{"issue":"1","key":"719_CR74","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3390\/molecules14010053","volume":"14","author":"I Spasojevic","year":"2008","unstructured":"Spasojevic I, Jelic S, Zakrzewska J, Bacic G. Decreased oxygen transfer capacity of erythrocytes as a cause of 5-fluorouracil related ischemia. Molecules. 2008;14(1):53\u201367. https:\/\/doi.org\/10.3390\/molecules14010053.","journal-title":"Molecules."},{"issue":"5","key":"719_CR75","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s11936-017-0535-5","volume":"19","author":"DE Giza","year":"2017","unstructured":"Giza DE, Boccalandro F, Lopez-Mattei J, Iliescu G, Karimzad K, Kim P, et al. Ischemic heart disease: special considerations in cardio-oncology. Curr Treat Options Cardiovasc Med. 2017;19(5):37. https:\/\/doi.org\/10.1007\/s11936-017-0535-5.","journal-title":"Curr Treat Options Cardiovasc Med"},{"issue":"11","key":"719_CR76","doi-asserted-by":"publisher","first-page":"2779","DOI":"10.1253\/circj.cj-66-0098","volume":"78","author":"Group JCSJW","year":"2014","unstructured":"Group JCSJW. Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2013). Circ J. 2014;78(11):2779\u2013801. https:\/\/doi.org\/10.1253\/circj.cj-66-0098.","journal-title":"Circ J"},{"issue":"18","key":"719_CR77","doi-asserted-by":"publisher","first-page":"4545","DOI":"10.1158\/1078-0432.CCR-16-0638","volume":"22","author":"G Ison","year":"2016","unstructured":"Ison G, Beaver JA, McGuinn WD Jr, Palmby TR, Dinin J, Charlab R, et al. FDA approval: uridine triacetate for the treatment of patients following fluorouracil or capecitabine overdose or exhibiting early-onset severe toxicities following administration of these Drugs. Clin Cancer Res. 2016;22(18):4545\u20139. https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-0638.","journal-title":"Clin Cancer Res"},{"issue":"1","key":"719_CR78","first-page":"41","volume":"6","author":"MW Saif","year":"2008","unstructured":"Saif MW, Tomita M, Ledbetter L, Diasio RB. Capecitabine-related cardiotoxicity: recognition and management. J Support Oncol. 2008;6(1):41\u20138.","journal-title":"J Support Oncol"},{"issue":"5","key":"719_CR79","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1093\/annonc\/mdf035","volume":"13","author":"N Frickhofen","year":"2002","unstructured":"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(5):797\u2013801. https:\/\/doi.org\/10.1093\/annonc\/mdf035.","journal-title":"Ann Oncol"},{"issue":"3","key":"719_CR80","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1345\/aph.1E252","volume":"39","author":"S Aksoy","year":"2005","unstructured":"Aksoy S, Karaca B, Dincer M, Yalcin S. Common etiology of capecitabine and fluorouracil-induced coronary vasospasm in a colon cancer patient. Ann Pharmacother. 2005;39(3):573\u20134. https:\/\/doi.org\/10.1345\/aph.1E252.","journal-title":"Ann Pharmacother"},{"key":"719_CR81","unstructured":"Clavel M, Simeone P, Grivet B. Cardiac toxicity of 5-fluorouracil. Review of the literature, 5 new cases. Presse Med. 1988;17(33):1675\u20138 [in French]."},{"issue":"4","key":"719_CR82","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1097\/00000441-198710000-00004","volume":"294","author":"B Patel","year":"1987","unstructured":"Patel B, Kloner RA, Ensley J, Al-Sarraf M, Kish J, Wynne J. 5-Fluorouracil cardiotoxicity: left ventricular dysfunction and effect of coronary vasodilators. Am J Med Sci. 1987;294(4):238\u201343. https:\/\/doi.org\/10.1097\/00000441-198710000-00004.","journal-title":"Am J Med Sci"},{"issue":"5","key":"719_CR83","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/sj.bjc.6601224","volume":"89","author":"Y Yamada","year":"2003","unstructured":"Yamada Y, Hamaguchi T, Goto M, Muro K, Matsumura Y, Shimada Y, et al. Plasma concentrations of 5-fluorouracil and F-beta-alanine following oral administration of S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, as compared with protracted venous infusion of 5-fluorouracil. Br J Cancer. 2003;89(5):816\u201320. https:\/\/doi.org\/10.1038\/sj.bjc.6601224.","journal-title":"Br J Cancer"},{"issue":"8","key":"719_CR84","first-page":"1482","volume":"9","author":"K Kikuchi","year":"1982","unstructured":"Kikuchi K, Majima S, Murakami M. Clinical survey on cardiotoxicity of tegafur (FT-207)--compilation of a nationwide survey. Gan To Kagaku Ryoho. 1982;9(8):1482\u20138.","journal-title":"Gan To Kagaku Ryoho"},{"issue":"1","key":"719_CR85","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3816\/CCC.2002.n.010","volume":"2","author":"JC Marsh","year":"2002","unstructured":"Marsh JC, Catalano P, Huang J, Graham DL, Cornfeld MJ, O'Dwyer PJ, et al. Eastern Cooperative Oncology Group phase II trial (E4296) of oral 5-fluorouracil and eniluracil as a 28-day regimen in metastatic colorectal cancer. Clin Colorectal Cancer. 2002;2(1):43\u201350. https:\/\/doi.org\/10.3816\/CCC.2002.n.010.","journal-title":"Clin Colorectal Cancer"},{"key":"719_CR86","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1186\/s12885-016-2409-8","volume":"16","author":"F Petrelli","year":"2016","unstructured":"Petrelli F, Barni S, Bertocchi P, Zaniboni A. TAS-102, the first \u201ccardio-gentle\u201d fluoropyrimidine in the colorectal cancer landscape? BMC Cancer. 2016;16:386. https:\/\/doi.org\/10.1186\/s12885-016-2409-8.","journal-title":"BMC Cancer"},{"issue":"21","key":"719_CR87","doi-asserted-by":"publisher","first-page":"3713","DOI":"10.1111\/bph.13725","volume":"174","author":"P Altieri","year":"2017","unstructured":"\u2022 Altieri P, Murialdo R, Barisione C, Lazzarini E, Garibaldi S, Fabbi P, et al. 5-fluorouracil causes endothelial cell senescence: potential protective role of glucagon-like peptide 1. Br J Pharmacol. 2017;174(21):3713\u201326. https:\/\/doi.org\/10.1111\/bph.13725 Endothelial cell senescence induced by 5-FU was found to be prevented by GLP-1 in a cell-based study.","journal-title":"Br J Pharmacol"},{"issue":"5","key":"719_CR88","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1517\/17425255.2015.1027684","volume":"11","author":"S Matsusaka","year":"2015","unstructured":"Matsusaka S, Lenz HJ. Pharmacogenomics of fluorouracil -based chemotherapy toxicity. Expert Opin Drug Metab Toxicol. 2015;11(5):811\u201321. https:\/\/doi.org\/10.1517\/17425255.2015.1027684.","journal-title":"Expert Opin Drug Metab Toxicol"}],"container-title":["Current Treatment Options in Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-020-0719-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11864-020-0719-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-020-0719-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T01:22:17Z","timestamp":1616116937000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11864-020-0719-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,19]]},"references-count":88,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["719"],"URL":"https:\/\/doi.org\/10.1007\/s11864-020-0719-1","relation":{},"ISSN":["1527-2729","1534-6277"],"issn-type":[{"value":"1527-2729","type":"print"},{"value":"1534-6277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,19]]},"assertion":[{"value":"19 March 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"Taro Shiga received personal fees from Daiichi-Sankyo and Bayer. Makoto Hiraide declares that he has no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}],"article-number":"27"}}