title: Clinical Pharmacokinetics of Tegafur Administered with Epirubicin and Cisplatin in Patients with Advanced Gastric Cancer.
abstract: OBJECTIVE
  Tegafur, an oral prodrug of 5-fluorouracil (5-FU), has been used in the treatment of gastric cancers. UFT (tegafur + uracil) has been developed to enhance the efficacy of tegafur. This study was conducted to assess the pharmacokinetics (PK) of tegafur in gastric cancer patients given the ECU-E regimen (epirubicin, cisplatin, UFT-E, an enteric-coated formula of UFT). A preliminary evaluation of antitumor efficacy and toxicity of ECU-E regimen was also performed.
  
  
  METHODS
  Of the 32 gastric cancer patients registered for the ECU-E regimen, 8 participated in the PK study. The plasma concentration of tegafur was determined using HPLC.
  
  
  RESULTS
  Seven out of the 8 patients were evaluable for response after 2 cycles, and showed 3 partial responses, 1 stable disease and 3 progressive diseases. No major toxicities were observed. Plasma profiles of the tegafur after the first dose showed significant differences in the amount and rate of absorption, i.e., rapid absorption group vs. slow absorption group. The level of C(max) in the rapid absorption group was 1.8 fold higher, and the AUC(0-5h) 4 fold greater, than those in the slow absorption group, nonetheless, the steady state concentrations showed no significant difference. These data indicate that the different absorption rates may not affect the overall exposure to tegafur. The patients with low Cp(ss, peak) showed poor efficacy compared to those with high Cp(ss, peak), suggesting that the concentration of tegafur may be one of the pharmacodynamic determinants in patients administered with ECU-E.
  
  
  CONCLUSIONS
  This study evaluated the pharmacokinetics of tegafur in gastric patients given the ECU-E regimen, and provides preliminary data on the relationship between the plasma tegafur level and the efficacy, which warrants further evaluation.
authors.forename: Jin Hyung
authors.initials: JH
authors.lastname: Kang
authors.forename: Yoo Lim
authors.initials: YL
authors.lastname: Kim
authors.forename: Hea Kyoung
authors.initials: HK
authors.lastname: Cho
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Cha
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Hong
authors.forename: Kyung Shik
authors.initials: KS
authors.lastname: Lee
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kuh
keywords: Pharmacokinetics; Stomach neoplasm; Tegafur; Uracil