title: S-1 as a core anticancer fluoropyrimidine agent.
abstract: BACKGROUND
  5-FU is a core anticancer agent for GI and other malignancies, and infusional 5-FU regimens have been widely utilized. Orally administrable fluoropyrimidine prodrugs have been developed to enhance the anticancer efficacy of 5-FU and to reduce its adverse reactions.
  
  
  METHODS
  S-1 is an FT-based oral 5-FU prodrug in combination with a DPD inhibitor (CDHP) and an OPRT inhibitor (Oxo), which exerts the following effects: i) maintaining normal gut immunity, Oxo can decrease GI toxicities of 5-FU; ii) sustaining high plasma 5-FU concentrations, Cmax of FBAL after S-1 administration is extremely low, which dramatically decreases adverse reactions such as HFS, neurotoxicities and cardiotoxicities; iii) plasma 5-FU concentrations vary less extensively after S-1 administration and iv) S-1 can be safely administered to patients with DPD deficiency. Furthermore, the alternate-day S-1 administration can reduce the GI toxicities and myelotoxicities of 5-FU without reducing its anticancer efficacy, enabling patients to continue the oral administration for 6 - 12 months.
  
  
  CONCLUSIONS
  Replacement of regimens with infusional 5-FU and other fluoropyrimidines by the alternate-day S-1 administration may be recommended because the latter procedure is efficient for patients while sustaining the enhanced anticancer efficacy of 5-FU and without reducing its dose intensity.
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. k-miura@surg1.med.tohoku.ac.jp
authors.forename: Koh
authors.initials: K
authors.lastname: Miura
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Shirasaka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
authors.forename: Iwao
authors.initials: I
authors.lastname: Sasaki
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000208:ethnology; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D011355:Prodrugs / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011355:Prodrugs; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid