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生物标志物作为接受伊立替康和顺铂治疗的不可切除胃癌患者反应和预后的预测指标。

Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with irinotecan and cisplatin.

作者信息

Nagashima Fumio, Boku Narikazu, Ohtsu Atsushi, Yoshida Shigeaki, Hasebe Takahiro, Ochiai Atsushi, Sakata Yu, Saito Hiroshi, Miyata Yoshinori, Hyodo Ichinosuke, Ando Masahiko

机构信息

Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.

出版信息

Jpn J Clin Oncol. 2005 Dec;35(12):714-9. doi: 10.1093/jjco/hyi194. Epub 2005 Nov 22.

Abstract

BACKGROUND

Previously we reported that immunohistochemical examination of p53, bcl-2, glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and vascular endothelial growth factor (VEGF) in biopsy samples was a useful method for predicting clinical outcome of gastric cancer patients treated with 5-fluorouracil and cisplatin. Here, we investigated if these biological markers can predict chemoresponse and survival of unresectable gastric cancer patients treated with irinotecan and cisplatin.

METHODS

The subjects were 55 unresectable gastric cancer patients treated with irinotecan (70 mg/m(2), Days 1 and 15) and cisplatin (80 mg/m(2), Day 1). Expression of p53, bcl-2, VEGF was examined immunohistochemically in biopsy samples.

RESULTS

The overall response rate and the median survival time were 55% (30/55) and 321 days, respectively. Thirty patients with intestinal-type adenocarcinoma survived longer than 25 patients with diffuse-type (median survival time: 446, 259 days, P = 0.013). The favorable phenotypes for chemoresponse were p53-negative, bcl-2-negative and VEGF-positive, which were in accordance with previous findings. The response rate was significantly correlated with the total number of these favorable phenotypes (P = 0.043). The 39 patients having 2 or 3 favorable phenotypes (p53-negative, bcl-2-negative and VEGF-positive) survived longer than the remaining 16 patients (median survival time: 444, 259 days, P = 0.021). In the Cox model, the number of the favorable phenotypes showed a tendency to correlate with survival after adjustment for potentially prognostic factors such as histological type or performance status (P = 0.070).

CONCLUSIONS

Immunohistochemical examination of biological markers may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with irinotecan and cisplatin.

摘要

背景

此前我们报道,对活检样本中的p53、bcl-2、谷胱甘肽S-转移酶-pi(GST-pi)、胸苷酸合成酶(TS)和血管内皮生长因子(VEGF)进行免疫组化检查,是预测接受5-氟尿嘧啶和顺铂治疗的胃癌患者临床结局的一种有用方法。在此,我们研究了这些生物学标志物是否能预测接受伊立替康和顺铂治疗的不可切除胃癌患者的化疗反应和生存情况。

方法

研究对象为55例接受伊立替康(70 mg/m²,第1天和第15天)和顺铂(80 mg/m²,第1天)治疗的不可切除胃癌患者。对活检样本进行免疫组化检查,检测p53、bcl-2、VEGF的表达情况。

结果

总缓解率和中位生存时间分别为55%(30/55)和321天。30例肠型腺癌患者的生存期长于25例弥漫型患者(中位生存时间:446天、259天,P = 0.013)。化疗反应的有利表型为p53阴性、bcl-2阴性和VEGF阳性,这与之前的研究结果一致。缓解率与这些有利表型的总数显著相关(P = 0.043)。39例具有2种或3种有利表型(p53阴性、bcl-2阴性和VEGF阳性)的患者生存期长于其余16例患者(中位生存时间:444天、259天,P = 0.021)。在Cox模型中,在对组织学类型或体能状态等潜在预后因素进行校正后,有利表型的数量显示出与生存相关的趋势(P = 0.070)。

结论

对生物学标志物进行免疫组化检查可能有助于预测接受伊立替康和顺铂治疗的不可切除胃癌患者的临床结局。

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