Tegafur, gimeracil, oteracil (S-1)

Note: this drug is approved in Japan and Europe but not the US.

Mechanism of action

From the NCI Drug Dictionary: An orally bioavailable fluoropyrimidine antagonist composed of tegafur combined with two modulators of 5-flurouracil (5-FU) activity, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate, in a molar ratio of 1:0.4:1. Tegafur is a prodrug of 5-fluorouracil, an antimetabolite that inhibits thymidylate synthase, DNA synthesis and cell division, and competes with uridine triphosphate, thus inhibiting RNA and protein synthesis. CDHP is a reversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. Potassium oxonate preferentially localizes in the gut and inhibits the enzyme orotate phosphoribosyl-transferase (OPRT), thereby decreasing activation of 5-FU in the gut and activated 5-FU-related gastrointestinal toxicity.

Diseases for which it is used

• Breast cancer
• Cholangiocarcinoma
• Colon cancer
• Gallbladder cancer
• Gastric cancer
• Non-small cell lung cancer
  • Non-small cell lung cancer, squamous
• Pancreatic cancer
• Rectal cancer

History of changes in EMA indication

• 2011-03-14: Initial marketing authorization as Teysuno.

History of changes in PMDA indication

• 2005-11-14: New indication for the treatment of inoperable or recurrent breast cancer.
• 2006-08-10: New indication for pancreatic cancer.
• 2007-08-23: New indication for the treatment of biliary cancer in addition to gastric cancer, colorectal cancer, head and neck cancer, non-small cell lung cancer, and pancreatic cancer.
• 2007-08-23: New indication for the treatment of inoperable or relapsed breast cancer.
• 2022-11-24: New indication and a new dosage for the postoperative adjuvant treatment of hormone receptor(HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer with a high risk of recurrence.

Also known as

• Code name: S-1
• Brand name: Teysuno, TS-One, TS-1