Fixed dosing and pharmacokinetics of S-1 in Japanese cancer patients with large body surface areas

Ann Oncol. 2009 May;20(5):946-9. doi: 10.1093/annonc/mdn718. Epub 2009 Jan 15.

Abstract

Background: S-1 is an oral anticancer agent that combines tegafur (FT) with 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate. The recommended initial dose of S-1 is 120 mg/day for patients with a body surface area (BSA) of > or =1.5 m(2) in Japan.

Methods: We examined the effects of using this fixed dose on the pharmacokinetics of FT, CDHP, and active 5-fluorouracil (5-FU) on the basis of actual BSA. The pharmacokinetics was compared between patients with a BSA of 1.5-1.75 m(2) and those with a BSA of > or =1.75 m(2).

Results: The median areas under the time-concentration curves (AUCs) of 5-FU and CDHP were significantly lower in patients with a BSA of > or =1.75 m(2) than in those with a BSA of 1.5-1.75 m(2) (P = 0.005 and 0.006, respectively; Mann-Whitney U-test). There was no difference between the groups in the median AUC of FT.

Conclusion: Systemic exposure to 5-FU is significantly lower in Japanese cancer patients with a large BSA of >1.75 m(2) who received the recommended fixed dose of S-1.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Area Under Curve
  • Body Surface Area*
  • Drug Combinations
  • Drug Dosage Calculations
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / ethnology
  • Oxonic Acid / administration & dosage*
  • Oxonic Acid / pharmacokinetics*
  • Tegafur / administration & dosage*
  • Tegafur / pharmacokinetics*
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid