Tegafur/gimeracil/oteracil

The combination drug tegafur/gimeracil/oteracil (trade name Teysuno, and TS-1 in Japan[1]), also known as S-1,[2] is used for the treatment of advanced gastric cancer.[3] 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.[4]:213 It has not been approved by the FDA.[4]:213

Tegafur/gimeracil/oteracil
Combination of
TegafurAntineoplastic drug
GimeracilEnzyme inhibitor
OteracilEnzyme inhibitor
Clinical data
Trade namesTeysuno
AHFS/Drugs.comUK Drug Information
License data
Pregnancy
category
  • Contraindicated
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID

It is also being developed for the treatment of hepatocellular carcinoma.[5] and has activity in esophageal,(Perry Chapter 33) breast, cervical, and colorectal cancer.[6]

Within the medication, the molar ratio of the three components (tegafur:gimeracil:oteracil) is 1:1:0.4.[7]

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.[4]:213

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.[8]

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.[8]

  • Tegafur
  • Gimeracil
  • Oteracil potassium

References
  1. TS-1.jp, Taiho Pharmaceutical
  2. Liu TW, Chen LT (201). "S-1 with leucovorin for gastric cancer: how far can it go?". Lancet Oncol. 17: 12–4. doi:10.1016/S1470-2045(15)00478-7. PMID 26640038.
  3. UK Drug Information
  4. DeVita, DeVita; Lawrence, TS; Rosenberg, SA (2015). DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology (10th ed.). LWW. ISBN 978-1451192940.
  5. http://www.biocentury.com/BCIQ
  6. Miyamoto Y, Sakamoto Y, Yoshida N, Baba H (2014). "Efficacy of S-1 in colorectal cancer". Expert Opin Pharmacother. 15 (12): 1761–70. doi:10.1517/14656566.2014.937706. PMID 25032886.
  7. Peters GJ, Noordhuis P, Van Kuilenburg AB et al. (2003). "Pharmacokinetics of S-1, an oral formulation of ftorafur, oxonic acid and 5-chloro-2,4-dihydroxypyridine (molar ratio 1:0.4:1) in patients with solid tumors". Cancer Chemother. Pharmacol. 52 (1): 1–12. doi:10.1007/s00280-003-0617-9. PMID 12739060.CS1 maint: uses authors parameter (link)
  8. A. Klement (22 July 2013). "Dreier-Kombination gegen Magenkrebs: Teysuno". Österreichische Apothekerzeitung (in German) (15/2013): 23.


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