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Author Jin-Hyung Kang, M.D.1*, Yoo-Lim Kim, B.S.*, Hea-Kyoung Cho, Pharm.D.2, Eun-Sook Lee, Pharm.D.3, Soo Jin Cha, M.S.1, Young Sun Hong, M.D.1, Kyung Shik Lee, M.D.1 and Hyo-Jeong Kuh, Ph.D.4
Place of duty Catholic Research Institutes of Medical Science, 1Catholic Cancer Center, The Catholic University of Korea, 2Drug Information Institute, Sookmyung Women's University, 3Seoul National University Bundang Hospital, Gyeonggi, Korea
Title Clinical Pharmacokinetics of Tegafur Administered with Epirubicin and Cisplatin in Patients with Advanced Gastric Cancer
Publicationinfo Cancer Research and Treatment 2003 Jun; 035(03): 224-231.
Key_word Pharmacokinetics, Tegafur, Uracil, Stomach neoplasm
Full-Text
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 Cmax in the rapid absorption group was 1.8 fold higher, and the AUC0-5h 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 Cpss,peak showed poor efficacy compared to those with high Cpss,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. (Cancer Research and Treatment 2003;35:224 231)