{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:14:22Z","timestamp":1754144062382,"version":"3.41.2"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Servier Italia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Trifluridine\/tipiracil (FTD\/TPI), an oral fluoropyrimidine (FP) from the class of antimetabolites, approved for refractory metastatic colorectal cancer, is thought, to have no cardiac toxicity. The aim of this observational, prospective, multicenter study was to identify the incidence of cardiotoxicity of FTD\/TPI; secondary objectives were to evaluate whether patients with previous heart diseases or cardiovascular risk factors, who were treated with FTD\/TPI, were more susceptible to cardiotoxicity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>Patients received FTD\/TPI according to clinical practice and provided informed consent to participate in this prospective study. Any symptoms that occurred during the treatment were reported by patients using a daily questionnaire (patient-reported outcome). In the case of symptoms suspected of cardiotoxicity patients were investigated with an ECG, enzymes, and a cardiology examination. Quality of life (QoL) was analyzed using a GF7 item of the FACT-G questionnaire. Univariate and multivariate logistic regression models were used to test associations between covariates and cardiotoxicity. Changes in QoL were evaluated during treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Four out of seventy-seven patients had cardiotoxicity\u2005\u2265\u2005G3 according to the common terminology criteria for adverse events during FTD\/TPI treatment. There was: chest pain in 3 cases, and heart failure in one case. The overall incidence of cardiotoxicity was 5.19%. By univariate analysis, obesity, and anemia were demonstrated to be risk factors of cardiotoxicity, while with multivariate analysis, only hemoglobin levels were statistically associated with cardiotoxicity. Average QoL after treatment was not significantly decreased as compared to average basal QoL.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The risk of developing cardiotoxicity with FTD\/TPI is lower than with other FP but it is not negligible. Previous heart diseases or cardiovascular risk factors do not represent an increased risk of cardiotoxicity of FTD\/TPI. Further studies are needed to investigate this topic.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf178","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T04:28:40Z","timestamp":1752553720000},"source":"Crossref","is-referenced-by-count":0,"title":["Cartoon: multicenter prospective observational study of Cardiovascular Toxicity of Trifluridine\/Tipiracil in metastatic colorectal cancer"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-9706","authenticated-orcid":false,"given":"Francesco","family":"Leone","sequence":"first","affiliation":[{"name":"Dipartimento di Oncologia, Ospedale degli Infermi ASL BI , Ponderano ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Fiamma","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche, Universit\u00e0 degli Studi di Torino , Torino ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9880-8459","authenticated-orcid":false,"given":"Francesca","family":"Crivelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, Ospedale degli Infermi ASL BI , Ponderano ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam Katja","family":"Paris","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, Ospedale degli Infermi ASL BI , Ponderano ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura Giovanna","family":"Forti","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, AOU Maggiore della Carit\u00e0 , Novara ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Pia","family":"Brizzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia Medica, AOU San Luigi Gonzaga , Orbassano (TO) ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Sperti","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario di Oncologia, AO Ordine Mauriziano , Torino ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Laface","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, Ospedale degli Infermi ASL BI , Ponderano ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nastassja","family":"Tober","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, AOU Maggiore della Carit\u00e0 , Novara ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Salerno","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche, Universit\u00e0 degli Studi di Torino , Torino ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena Silvia","family":"Traverso","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, AOU Alessandria ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Parlagreco","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, AO S. Croce e Carle , Cuneo ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Nepote","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia Medica, AOU San Luigi Gonzaga , Orbassano (TO) ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Giuli","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, ASL VCO , Verbania ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Bonessio","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, Ospedale degli Infermi ASL BI , Ponderano ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Nicol\u00ec","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, Ospedale degli Infermi ASL BI , Ponderano ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Bertola","sequence":"additional","affiliation":[{"name":"Dipartimento di Cardiologia, Ospedale degli Infermi ASL BI , Ponderano ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Montagnani","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia, Ospedale degli Infermi ASL BI , Ponderano ,","place":["Italia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"2025071500283974800_CIT0001","doi-asserted-by":"publisher","first-page":"31","DOI":"10.3892\/or.2022.8468","article-title":"Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: a prospective observational trial (CHECKPOINT)","volume":"49","author":"Lombardi","year":"2023","journal-title":"Oncol Rep"},{"key":"2025071500283974800_CIT0002","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/annonc\/mdu055","article-title":"Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk","volume":"25","author":"Lestuzzi","year":"2014","journal-title":"Ann Oncol"},{"key":"2025071500283974800_CIT0003","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1177\/0003319716637516","article-title":"Usefulness of Heart-Type Fatty Acid-Binding Protein and Myocardial Performance Index for Early Detection of 5-Fluorouracil Cardiotoxicity","volume":"68","author":"Turan","year":"2017","journal-title":"Angiology"},{"key":"2025071500283974800_CIT0004","doi-asserted-by":"publisher","first-page":"e158","DOI":"10.1093\/oncolo\/oyab035","article-title":"Cardiotoxicity from capecitabine chemotherapy: prospective study of incidence at rest and during physical exercise","volume":"27","author":"Lestuzzi","year":"2022","journal-title":"Oncologist"},{"issue":"2022","key":"2025071500283974800_CIT0005","doi-asserted-by":"publisher","first-page":"4229","DOI":"10.1093\/eurheartj\/ehac244","article-title":"ESC Guidelines on cardiooncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)","volume":"43","author":"Lyon","year":"2022"},{"key":"2025071500283974800_CIT0006","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"volume-title":"Common Terminology Criteria for Adverse Events (CTCAE) Version 5","year":"2017","author":"US Department of Health and Human Services, National Institutes of Health, National Cancer Institute","key":"2025071500283974800_CIT0007"},{"key":"2025071500283974800_CIT0008","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1093\/annonc\/mdf108","article-title":"Incidence of cardiotoxicity with the oral fluoropyrimidine capecitabine is typical of that reported with 5-fluorouracil","volume":"13","author":"Van Cutsem","year":"2002","journal-title":"Ann Oncol"},{"key":"2025071500283974800_CIT0009","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1186\/s12885-016-2409-8","article-title":"TAS-102, the first \u201ccardio-gentle\u201d fluoropyrimidine in the colorectal cancer landscape","volume":"16","author":"Petrelli","year":"2016","journal-title":"BMC Cancer"},{"key":"2025071500283974800_CIT0010","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1002\/cncr.22125","article-title":"Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors","volume":"107","author":"Hong","year":"2006","journal-title":"Cancer"},{"key":"2025071500283974800_CIT0011","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s10637-008-9142-3","article-title":"Phase 1 study of TAS-102 administered once daily on a 5-day-per-week schedule in patients with solid tumors","volume":"26","author":"Overman","year":"2008","journal-title":"Invest New Drugs"},{"key":"2025071500283974800_CIT0012","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1080\/07357900802087242","article-title":"Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors","volume":"26","author":"Overman","year":"2008","journal-title":"Cancer Invest"},{"key":"2025071500283974800_CIT0013","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/bjc.2012.274","article-title":"Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours","volume":"107","author":"Doi","year":"2012","journal-title":"Br J Cancer"},{"key":"2025071500283974800_CIT0014","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1007\/s00280-016-3031-9","article-title":"Phase 1 study of cardiac safety of TAS-102 in patients with advanced solid tumors","volume":"77","author":"Bendell","year":"2016","journal-title":"Cancer Chemother Pharmacol"},{"key":"2025071500283974800_CIT0015","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/S1470-2045(12)70345-5","article-title":"TAS-102 monotherapy for pretreated metastatic colorectal cancer: a doubleblind, randomised, placebo-controlled phase 2 trial","volume":"13","author":"Yoshino","year":"2012","journal-title":"Lancet Oncol"},{"key":"2025071500283974800_CIT0016","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1056\/NEJMoa1414325","article-title":"RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer","volume":"372","author":"Mayer","year":"2015","journal-title":"N Engl J Med"},{"key":"2025071500283974800_CIT0017","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12885-022-10489-4","article-title":"Safety and efficacy of trifluridine\/tipiracil in previously treated metastatic colorectal cancer: final results from the phase IIIb single-arm PRECONNECT study by duration of therapy","volume":"23","author":"Taieb","year":"2023","journal-title":"BMC Cancer"},{"key":"2025071500283974800_CIT0018","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1001\/jama.2017.7156","article-title":"Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment","volume":"318","author":"Basch","year":"2017","journal-title":"JAMA"},{"key":"2025071500283974800_CIT0019","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1016\/j.annonc.2022.04.007","article-title":"ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. The role of patient-reported outcome measures in the continuum of cancer clinical care: ESMO Clinical Practice Guideline","volume":"33","author":"Di Maio","year":"2022","journal-title":"Ann Oncol"},{"author":"National Institutes of Health, National Cancer Institute, Division of Cancer Control & Population Sciences","key":"2025071500283974800_CIT0020","article-title":"Patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE\u2122)"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/7\/oyaf178\/63758583\/oyaf178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/7\/oyaf178\/63758583\/oyaf178.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T04:28:41Z","timestamp":1752553721000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyaf178\/8201159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":20,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7,4]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyaf178","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"type":"print","value":"1083-7159"},{"type":"electronic","value":"1549-490X"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,7]]},"article-number":"oyaf178"}}