title: Pharmacokinetic study of weekly (days 1-5) low-dose S-1 in patients with non-small-cell lung cancer.
abstract: BACKGROUND
  S-1, an oral fluoropyrimidine, is usually given for 4 weeks (80 mg/m2/day) followed by a 2-week rest. However, compliance with this regimen is unsatisfactory because of adverse events such as leukopenia, anorexia, and nausea. To reduce adverse effects and improve compliance, we studied a "5-day on/2-day off" low-dose regimen of S-1 and evaluated pharmacokinetics in patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Twelve patients with NSCLC were divided into 2 groups and received S-1 in a dose of 25 mg twice daily (level 1, n = 6) or 40 mg twice daily (level 2, n = 6) for 5 consecutive days followed by a 2-day rest (5 days on/2 days off) every week. Plasma 5-fluorouracil (5-FU) concentrations were measured.
  
  
  RESULTS
  The maximum concentration in plasma and the area under the plasma concentration-time curve from 0 to 9 h were respectively 55.3 ± 21.1 ng/ml and 290.2 ± 95.7 ng·hr/ml for level 1, as compared with 104.2 ± 33.5 ng/ml and 541.9 ± 232.3 ng·hr/ml for level 2. These values were similar to those previously reported for a continuous intravenous infusion of 5-FU. Adverse events were grade 1 fatigue (n = 1 in each group) and anorexia (n = 1 in each group).
  
  
  CONCLUSIONS
  A "5-day on/2-day off" low-dose (40 mg twice daily) regimen of S-1 is feasible for the treatment of NSCLC, with acceptable plasma 5-FU concentrations and minimal adverse effects. A phase II or III trial of this regimen in an adjuvant setting is warranted in patients with NSCLC.
authors.affiliation: Department of Thoracic Surgery, Kyoto University Hospital, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan. tshoji@kuhp.kyoto-u.ac.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shoji
authors.forename: Makoto
authors.initials: M
authors.lastname: Sonobe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakai
authors.forename: Takuji
authors.initials: T
authors.lastname: Fujinaga
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Sato
authors.forename: Fengshi
authors.initials: F
authors.lastname: Chen
authors.forename: Ryo
authors.initials: R
authors.lastname: Miyahara
authors.forename: Toru
authors.initials: T
authors.lastname: Bando
authors.forename: Hiromi
authors.initials: H
authors.lastname: Wada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010349:Patient Compliance; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; C104201:gimeracil