Relative Dose Intensity and Clinical Outcomes of Using Trifluridine/Tipiracil With or Without Bevacizumab in Patients Aged ≥75 Years With Advanced or Recurrent Colorectal Cancer: A Single-Center Retrospective Study

Relative Dose Intensity and Clinical Outcomes of Using Trifluridine/Tipiracil With or Without Bevacizumab in Patients Aged ≥75 Years With Advanced or Recurrent Colorectal Cancer: A Single-Center Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Relative Dose Intensity and Clinical Outcomes of Using Trifluridine/Tipiracil With or Without Bevacizumab in Patients Aged ≥75 Years With Advanced or Recurrent Colorectal Cancer: A Single-Center Retrospective Study Aiko Tomiuchi, Michio Kimura, Yoshiaki Ikeda, Eiseki Usami This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9299083/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Purpose: Evidence regarding treatment intensity, tolerability, and outcomes of using trifluridine/tipiracil (FTD/TPI) with or without bevacizumab (BV) in older patients with metastatic colorectal cancer (mCRC) is limited. We compared relative dose intensity (RDI), toxicity, and survival between FTD/TPI monotherapy and FTD/TPI plus BV, and examined the relationship between RDI and overall survival (OS) in older patients. Methods: In this single-center retrospective study, patients aged ≥ 75 years with unresectable or recurrent mCRC who received FTD/TPI monotherapy or FTD/TPI plus BV were included. The primary endpoint was RDI; secondary endpoints included treatment exposure, adverse events, achieving RDI ≥ 80%, and OS. Landmark analysis at two treatment cycles and multivariable Cox regression were used to assess the independent effect of the RDI on OS. Results: Forty-nine patients were included. Median RDI was 72.9% versus 74.8%, with no significant difference in achieving RDI ≥ 80%. Grade ≥ 3 neutropenia occurred in 60.5% vs. 81.8% of patients. BV-related hypertension and proteinuria were more frequent in the combination group. The median OS was longer in the combination therapy group (557 vs. 253 days). RDI ≥ 80% was not associated with OS in landmark or Cox regression analyses. Age and baseline hemoglobin levels were independent prognostic factors. Conclusions: FTD/TPI monotherapy and FTD/TPI + BV had similar RDI but different toxicity profiles. RDI ≥ 80% did not independently predict OS. In older patients with mCRC, treatment selection, tolerability, and patient-specific factors may be more important than strict dose intensity. These findings suggest that individualized treatment strategies may be important, although further prospective studies are warranted. older patients colorectal cancer trifluridine/tipiracil (FTD/TPI) Bevacizumab relative dose intensity (RDI) tolerability Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Apr, 2026 Editor assigned by journal 17 Apr, 2026 Submission checks completed at journal 10 Apr, 2026 First submitted to journal 02 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9299083","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":625243762,"identity":"fd1c567f-65fe-4d4c-b395-3e9b004e0118","order_by":0,"name":"Aiko Tomiuchi","email":"","orcid":"","institution":"Kinjo Gakuin University","correspondingAuthor":false,"prefix":"","firstName":"Aiko","middleName":"","lastName":"Tomiuchi","suffix":""},{"id":625243763,"identity":"e87322ca-3274-47a8-827a-f43ffa1819c0","order_by":1,"name":"Michio Kimura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYBACCWYGZoYEBgk7NvkDQG4FA4MBVIaZgBabZH4JEPcMMVogcmmMM2cAKcY2hBacQLKdO9ngYc5hZoPbvQc/fJx3WN6cvfkAw48KBnZzHFqkmXk3JyRuO8xncOdcsuTMbYcNd/YcS2DsOcPAbNmAXYscUMsBoBZmgwM5BtK82w4zbriRY8AMdCFQBL8Wxg0Hcox/8845bE9QC9RhIO/nmEnzNhxOJKhFspl3s0HiNmAg85wxs5xxLD15w5ljCQd7zkjg9IvE+bObJX9uA0Yle4/xjQ811rYbjjcffPCjwiYZV4ihg2YwCXSSRDLBCIKCOjjLjlgto2AUjIJRMOwBAMCrXL0uYFepAAAAAElFTkSuQmCC","orcid":"","institution":"Ogaki Municipal Hospital","correspondingAuthor":true,"prefix":"","firstName":"Michio","middleName":"","lastName":"Kimura","suffix":""},{"id":625243764,"identity":"80724652-1421-4b26-8537-23b3195c4979","order_by":2,"name":"Yoshiaki Ikeda","email":"","orcid":"","institution":"Kinjo Gakuin University","correspondingAuthor":false,"prefix":"","firstName":"Yoshiaki","middleName":"","lastName":"Ikeda","suffix":""},{"id":625243765,"identity":"435d2fd5-784a-4ffb-8615-b6e6e1c69d8e","order_by":3,"name":"Eiseki Usami","email":"","orcid":"","institution":"Ogaki Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Eiseki","middleName":"","lastName":"Usami","suffix":""}],"badges":[],"createdAt":"2026-04-02 06:41:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9299083/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9299083/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109153274,"identity":"a4bf4fd9-d5f4-4a01-ab91-001aedab4713","added_by":"auto","created_at":"2026-05-13 06:15:04","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":405089,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9299083/v1_covered_946ad143-c359-4e0e-95e8-568b9a2952d8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eRelative Dose Intensity and Clinical Outcomes of Using Trifluridine/Tipiracil With or Without Bevacizumab in Patients Aged ≥75 Years With Advanced or Recurrent Colorectal Cancer: A Single-Center Retrospective Study\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-gastrointestinal-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijgc","sideBox":"Learn more about [Journal of Gastrointestinal Cancer](https://www.springer.com/journal/12029)","snPcode":"12029","submissionUrl":"https://submission.nature.com/new-submission/12029/3","title":"Journal of Gastrointestinal Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"older patients, colorectal cancer, trifluridine/tipiracil (FTD/TPI), Bevacizumab, relative dose intensity (RDI), tolerability","lastPublishedDoi":"10.21203/rs.3.rs-9299083/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9299083/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eEvidence regarding treatment intensity, tolerability, and outcomes of using trifluridine/tipiracil (FTD/TPI) with or without bevacizumab (BV) in older patients with metastatic colorectal cancer (mCRC) is limited. We compared relative dose intensity (RDI), toxicity, and survival between FTD/TPI monotherapy and FTD/TPI plus BV, and examined the relationship between RDI and overall survival (OS) in older patients.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn this single-center retrospective study, patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years with unresectable or recurrent mCRC who received FTD/TPI monotherapy or FTD/TPI plus BV were included. The primary endpoint was RDI; secondary endpoints included treatment exposure, adverse events, achieving RDI\u0026thinsp;\u0026ge;\u0026thinsp;80%, and OS. Landmark analysis at two treatment cycles and multivariable Cox regression were used to assess the independent effect of the RDI on OS.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eForty-nine patients were included. Median RDI was 72.9% versus 74.8%, with no significant difference in achieving RDI\u0026thinsp;\u0026ge;\u0026thinsp;80%. Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 neutropenia occurred in 60.5% vs. 81.8% of patients. BV-related hypertension and proteinuria were more frequent in the combination group. The median OS was longer in the combination therapy group (557 vs. 253 days). RDI\u0026thinsp;\u0026ge;\u0026thinsp;80% was not associated with OS in landmark or Cox regression analyses. Age and baseline hemoglobin levels were independent prognostic factors.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eFTD/TPI monotherapy and FTD/TPI\u0026thinsp;+\u0026thinsp;BV had similar RDI but different toxicity profiles. RDI\u0026thinsp;\u0026ge;\u0026thinsp;80% did not independently predict OS. In older patients with mCRC, treatment selection, tolerability, and patient-specific factors may be more important than strict dose intensity. These findings suggest that individualized treatment strategies may be important, although further prospective studies are warranted.\u003c/p\u003e","manuscriptTitle":"Relative Dose Intensity and Clinical Outcomes of Using Trifluridine/Tipiracil With or Without Bevacizumab in Patients Aged ≥75 Years With Advanced or Recurrent Colorectal Cancer: A Single-Center Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-13 06:13:30","doi":"10.21203/rs.3.rs-9299083/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-18T01:43:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-18T01:42:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-10T06:54:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Gastrointestinal Cancer","date":"2026-04-02T06:31:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-gastrointestinal-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijgc","sideBox":"Learn more about [Journal of Gastrointestinal Cancer](https://www.springer.com/journal/12029)","snPcode":"12029","submissionUrl":"https://submission.nature.com/new-submission/12029/3","title":"Journal of Gastrointestinal Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"cef9acb2-4d7e-4ea3-9cf3-346fdd1ce38a","owner":[],"postedDate":"May 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T06:13:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-13 06:13:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9299083","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9299083","identity":"rs-9299083","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}