Tegafur/gimeracil/oteracil
The combination drug tegafur/gimeracil/oteracil (trade name Teysuno, and TS-1 in Japan), also known as S-1, is used for the treatment of advanced gastric cancer. It is labelled for use in combination with cisplatin in many European countries, and for head and neck cancer, colorectal cancer, non–small-cell lung, breast, pancreatic, and biliary tract cancers in several countries in Asia. It has not been approved by the FDA.

It is also being developed for the treatment of hepatocellular carcinoma. and has activity in esophageal,(Perry Chapter 33) breast, cervical, and colorectal cancer.

Within the medication, the molar ratio of the three components (tegafur:gimeracil:oteracil) is 1:1:0.4.

The maximum tolerated dose differed between Asian and Caucasian populations (80 mg/m2 and 25 mg/m2 respectively), perhaps due to differences in CYP2A6 genotype.

Mechanism of action
Tegafur is the actual chemotherapeutic agent. It is a prodrug of the active substance fluorouracil (5-FU).

Gimeracil inhibits the degradation of fluorouracil by reversibly blocking the dehydrogenase enzyme dihydropyrimidine dehydrogenase (DPD). This results in higher 5-FU levels and a prolonged half-life of the substance.

Oteracil mainly stays in the gut because of its low permeability, where it reduces the production of 5-FU by blocking the enzyme orotate phosphoribosyltransferase. Lower 5-FU levels in the gut result in a lower gastrointestinal toxicity.