Clinical Pharmacokinetics of Tegafur Administered with Epirubicin and Cisplatin in Patients with Advanced Gastric Cancer

Kang, Jin Hyung; Kim, Yoo Lim; Cho, Hea Kyoung; Lee, Eun Sook; Cha, Soo Jin; Hong, Young Sun; Lee, Kyung Shik; Kuh, Hyo Jeong

Abstract

PURPOSE
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. MATERIALS AND 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. CONCLUSION: 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.