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二氢嘧啶脱氢酶(DPD)免疫反应性在采用新型DPD抑制性氟嘧啶S-1治疗的胃硬癌中的临床应用

Clinical application of immunoreactivity of dihydropyrimidine dehydrogenase (DPD) in gastric scirrhous carcinoma treated with S-1, a new DPD inhibitory fluoropyrimidine.

作者信息

Shimizu Toshio, Yamada Yasuhide, Yasui Hisateru, Shirao Kuniaki, Fukuoka Masahiro

机构信息

Department of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.

出版信息

Anticancer Res. 2005 Jul-Aug;25(4):2997-3001.

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.

摘要

背景

已开发出一种针对重组人二氢嘧啶脱氢酶(DPD)的高度特异性抗体,用于免疫组织化学评估肿瘤中的DPD表达。据报道,一种新型口服DPD抑制性氟嘧啶(DIF),即S-1,对胃硬癌有效。

患者与方法

在本研究中,对61例接受一线氟嘧啶类化疗(S-1:DIF,5-氟尿嘧啶:非DIF)治疗的胃硬癌患者,研究活检标本中DPD免疫反应性与化疗效果之间的关系。

结果

S-1组中,DPD阳性肿瘤患者的缓解率显著高于DPD阴性肿瘤患者(45.5%,10.0%:p<0.05),而5-氟尿嘧啶组中DPD阳性肿瘤患者与DPD阴性肿瘤患者的缓解率分别为0%和5.6%(p = 0.398)。根据中位生存时间,S-1组中DPD阳性肿瘤患者(364天)与DPD阴性肿瘤患者(406天;p = 0.626)之间无显著差异,5-氟尿嘧啶组中DPD阳性肿瘤患者与DPD阴性肿瘤患者的中位生存时间分别为181天和256天(p = 0.543)。

结论

本研究表明,即使在DPD活性较高的胃硬癌中,S-1可能也有效。

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