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Clinical application of immunoreactivity of dihydropyrimidine dehydrogenase (DPD) in gastric scirrhous carcinoma treated with S-1, a new DPD inhibitory fluoropyrimidine
Authors:Shimizu Toshio  Yamada Yasuhide  Yasui Hisateru  Shirao Kuniaki  Fukuoka Masahiro
Affiliation:Department of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan. tosshimi@ncc.go.jp
Abstract:BACKGROUND: A highly specific antibody against recombinant human dihydropyrimidine dehydrogenase (DPD) has been developed to immunohistochemically assess DPD expression in tumors. A new oral DPD inhibitory fluoropyrimidine (DIF), S-1, is reportedly effective against gastric scirrhous carcinoma. PATIENTS AND METHODS: In this study, the relationship between immunoreactivity to DPD in biopsy specimens and the effects of chemotherapy were investigated in 61 patients treated with first-line fluoropyrimidine-based chemotherapy (S-1:DIF, 5-FU:non-DIF) for gastric scirrhous carcinoma. RESULTS: The response rate was significantly higher in patients with DPD-positive tumors than in those with DPD-negative tumors in the S-1 group (45.5%, 10.0%: p < 0.05), as compared to the 5-FU group (0%, 5.6%: p = 0.398). According to the median survival time, there was no significant difference between patients with DPD-positive tumors (364 days) and those with DPD-negative tumors (406 days; p = 0.626) in either the S-1 group or the 5-FU group (181 days and 256 days, respectively; p = 0.543). CONCLUSION: This study indicates that S-1 may be effective even in gastric scirrhous carcinoma with a high level of DPD activity.
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