{"entity":{"id":"trifluridine-tipiracil","kind":"drug","name":"Trifluridine/tipiracil","aka":[],"tldr":"An oral chemotherapy pill for bowel cancer that has stopped responding to everything else; with bevacizumab it extends life by about three months.","summary":"Trifluridine is incorporated into DNA; tipiracil blocks its breakdown. RECOURSE (2015) showed OS 7.1 vs 5.3 months alone; SUNLIGHT (2023) showed 10.8 vs 7.5 months with bevacizumab. Also approved in gastric cancer (TAGS). Neutropenia is the main toxicity; works even after 5-FU resistance because of a different mechanism.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Trifluridine/tipiracil","links":[{"label":"FDA label","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/207981s012lbl.pdf"},{"label":"NICE TA405: trifluridine-tipiracil for previously treated metastatic colorectal cancer","url":"https://www.nice.org.uk/guidance/ta405"},{"label":"NICE TA1008: trifluridine-tipiracil with bevacizumab after 2 systemic treatments","url":"https://www.nice.org.uk/guidance/ta1008"},{"label":"EMA Lonsurf","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/lonsurf"}],"tags":[],"related":[],"cancers":["colorectal","gastric"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":["servier","takeda"],"institutions":[],"pathways":[],"terms":[],"trials":["sunlight","circulate-japan","nct06199973","nct07361003","nct06873763","nct04701476","nct05919264","nct06992258","nct05405595","nct07280377","nct04626635","recourse","altair"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Lonsurf","code":"TAS-102","modality":"Cytotoxic chemotherapy (oral nucleoside)","mechanism":"Trifluridine misincorporation into DNA causes strand dysfunction; tipiracil inhibits thymidine phosphorylase to maintain exposure.","approvals":[{"region":"US","year":2015,"indication":"Refractory metastatic colorectal cancer"},{"region":"US","year":2019,"indication":"Refractory metastatic gastric/GEJ cancer (TAGS)"},{"region":"US","year":2023,"indication":"Refractory mCRC with bevacizumab"},{"region":"EU","year":2016,"indication":"Metastatic colorectal cancer after available therapies","note":"Lonsurf marketing authorisation issued 25 April 2016."},{"region":"England (NICE)","year":2016,"indication":"Previously treated metastatic colorectal cancer","note":"TA405, published 24 August 2016, recommends it within its marketing authorisation with the patient access scheme discount."},{"region":"England (NICE)","year":2024,"indication":"Metastatic colorectal cancer after two lines of treatment, with bevacizumab","note":"TA1008, published 25 September 2024, recommends the combination within its marketing authorisation subject to the commercial arrangement."}],"mechanismSteps":["Tipiracil blocks the enzyme that would destroy trifluridine, keeping blood levels up","Trifluridine is taken up by dividing cancer cells and converted to its active form","It is built into DNA in place of thymidine","The corrupted DNA cannot function and the cell dies"],"dosing":{"route":"Oral","schedule":"35 mg/m² twice daily on days 1-5 and 8-12 of a 28-day cycle","modifications":"Delay for neutrophils <1,500 or platelets <75,000","monitoring":"Complete blood count before each cycle and on day 15","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/207981s012lbl.pdf"},"toxicity":[{"event":"Neutropenia","note":"Most common grade 3-4 event; febrile neutropenia uncommon"},{"event":"Anaemia"},{"event":"Nausea, fatigue"}],"access":[],"regulatoryEvents":[{"date":"2015-09","type":"approval","region":"US","note":"RECOURSE"},{"date":"2023-08","type":"approval","region":"US","note":"SUNLIGHT combination"}]},"route":"/drugs/trifluridine-tipiracil/","neighbours":{"cancer":[{"id":"braf-v600e-colorectal","kind":"cancer","name":"BRAF V600E-mutant colorectal cancer","route":"/cancers/braf-v600e-colorectal/"},{"id":"colorectal","kind":"cancer","name":"Colorectal 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