{"entity":{"id":"tegafur-gimeracil-oteracil","kind":"drug","name":"Tegafur, gimeracil and oteracil (S-1)","aka":["S-1","TS-1"],"tldr":"Teysuno (S-1) is an oral chemotherapy combining a fluorouracil pro-drug with two protectors. It is a standard in Japan and approved in Europe for stomach cancer with cisplatin and for bowel cancer when other fluoropyrimidines cause hand-foot syndrome or heart problems.","summary":"S-1 has been a mainstay of gastric, pancreatic, colorectal and lung cancer treatment in Japan since 1999 (ACTS-GC established adjuvant S-1 in gastric cancer). The European Commission authorised Teysuno in March 2011 for advanced gastric cancer with cisplatin, on the FLAGS trial in which S-1 plus cisplatin was non-inferior to fluorouracil plus cisplatin with less toxicity, and in 2022 for metastatic colorectal cancer as monotherapy or with oxaliplatin or irinotecan, with or without bevacizumab, in patients who cannot continue another fluoropyrimidine because of hand-foot syndrome or cardiovascular toxicity. Because Western patients metabolise tegafur faster through CYP2A6 polymorphisms, doses differ from Japan. It is not approved in the US, where a trial of S-1 versus fluorouracil failed to show superiority. Diarrhoea, neutropenia and stomatitis are the main toxicities.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Tegafur/gimeracil/oteracil","links":[{"label":"EPAR (EMA)","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/teysuno"},{"label":"Uesaka et al., JASPAC 01 (Lancet 2016)","url":"https://doi.org/10.1016/S0140-6736(16)30583-9"},{"label":"Ueno et al., GEST (JCO 2013)","url":"https://doi.org/10.1200/JCO.2012.43.3680"}],"tags":["ema-list"],"related":["fluorouracil","capecitabine"],"cancers":["gastric","colorectal","pancreatic","resectable-pdac","metastatic-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":["taiho"],"institutions":[],"pathways":[],"terms":["prodrug"],"trials":["jaspac-01","nct07262567","nct00660894","nct03448549"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer: S-1 is the adjuvant standard in Japan on JASPAC 01 (five-year survival 44.1 against 24.4 percent with gemcitabine, hazard ratio 0.57) and non-inferior to gemcitabine in advanced disease in GEST (median 9.7 against 8.8 months, hazard ratio 0.96; the gemcitabine plus S-1 arm was not superior). The EU product Teysuno (marketing authorisation 14 March 2011) is licensed for gastric and colorectal cancer only, and Western patients metabolise tegafur differently, so the drug is not used for pancreatic cancer in Europe or the United States."],"brand":"Teysuno","modality":"Oral fluoropyrimidine combination (antimetabolite)","mechanism":"Tegafur is a fluorouracil prodrug; gimeracil inhibits dihydropyrimidine dehydrogenase to sustain fluorouracil levels, and oteracil blocks phosphorylation of fluorouracil in the gut to reduce diarrhoea.","approvals":[{"region":"JP","year":1999,"indication":"Gastric cancer; later colorectal, head and neck, lung, pancreatic, biliary and breast cancer (TS-1)"},{"region":"EU","year":2011,"indication":"Advanced gastric cancer with cisplatin; metastatic colorectal cancer intolerant of other fluoropyrimidines added 2022 (Teysuno)"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/tegafur-gimeracil-oteracil/","neighbours":{"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"company":[{"id":"taiho","kind":"company","name":"Taiho Pharmaceutical (Otsuka)","route":"/companies/taiho/"}],"term":[{"id":"prodrug","kind":"term","name":"Prodrug","route":"/terms/prodrug/"}],"trial":[{"id":"nct07561775","kind":"trial","name":"Adebrelimab Plus S-1 for Resected Cholangiocarcinoma","route":"/trials/nct07561775/"},{"id":"nct06662877","kind":"trial","name":"Anlotinib Plus Nab-Paclitaxels and S-1 for Patients with Advanced Biliary Tract Cancer As Second-Line Treatment","route":"/trials/nct06662877/"},{"id":"ascot-jcog1202","kind":"trial","name":"ASCOT (JCOG1202)","route":"/trials/ascot-jcog1202/"},{"id":"nct06901622","kind":"trial","name":"Camrelizumab and Chemotherapy With or Without Anlotinib as First-line Treatment for Advanced Gallbladder Cancer and Extrahepatic Cholangiocarcinoma","route":"/trials/nct06901622/"},{"id":"nct05451290","kind":"trial","name":"Camrelizumab Plus Apatinib in Combination With GEMOX (Gemcitabine and Oxaliplatin ) in Patients With Locally Advanced Biliary Tract Cancer","route":"/trials/nct05451290/"},{"id":"nct06490107","kind":"trial","name":"Durvalumab Combined With S-1 as Adjuvant Therapy of Resectable BTC","route":"/trials/nct06490107/"},{"id":"nct07636824","kind":"trial","name":"Efficacy and Safety of Postoperative Concurrent Chemoradiotherapy for Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma: A Multicenter Prospective Phase II Study","route":"/trials/nct07636824/"},{"id":"nct06383078","kind":"trial","name":"HR070803 in Combination With Oxaliplatin, S-1 Versus NALIRIFOX as Adjuvant Therapy for Pancreatic Cancer","route":"/trials/nct06383078/"},{"id":"jaspac-01","kind":"trial","name":"JASPAC 01","route":"/trials/jaspac-01/"},{"id":"nct06571461","kind":"trial","name":"Liposomal Irinotecan in Combination With Oxaliplatin and S-1 Versus Gemcitabine Combined With Capecitabine as Postoperative Adjuvant Therapy for Pancreatic Canc","route":"/trials/nct06571461/"},{"id":"nct06903273","kind":"trial","name":"Neoadjuvant Tislelizumab, Gemcitabine, Cisplatin and S-1 for Resectable High-risk Cholangiocarcinoma","route":"/trials/nct06903273/"},{"id":"nct07262567","kind":"trial","name":"Phase III Study to Compare GFH375 and Chemotherapy in Patients With KRAS G12D-Mutant Metastatic Pancreatic Cancer","route":"/trials/nct07262567/"},{"id":"nct07745790","kind":"trial","name":"Safety and Efficacy of Multimodal Thermal Therapy (MTT) Combined With KRAS G12V mRNA Vaccine, S-1, and Sintilimab in Patients With Metastatic Pancreatic Cancer","route":"/trials/nct07745790/"},{"id":"nct06166589","kind":"trial","name":"Second-line Zimberelimab and SIRIOX Chemotherapy for Patient With Previously AG Chemotherapy Treated Pancreatic Cancer","route":"/trials/nct06166589/"},{"id":"nct03448549","kind":"trial","name":"SOX Versus XELOX as Adjuvant Chemotherapy for Stage III Colorectal Cancer Patients","route":"/trials/nct03448549/"},{"id":"nct00660894","kind":"trial","name":"Tegafur-Uracil and Leucovorin or S-1 in Treating Patients With Stage III Colon Cancer That Has Been Completely Removed by Surgery","route":"/trials/nct00660894/"}]}}