ERCC1蛋白表达在晚期胃癌含铂一线及替吉奥维持治疗中的作用

Role of ERCC1 protein expression in advanced gastric cancer treated with first-line platinum-based chemotherapy and S-1 maintenance chemotherapy

目的探讨切除修复交叉互补基因1（ERCC1）蛋白在晚期胃癌组织中表达水平与一线奥沙利铂联合替吉奥（SOX）方案化疗疗效和预后关系,观察低剂量替吉奥胶囊在一线化疗后维持治疗对患者生存期的影响及其安全性。方法85例初治Ⅳ期胃癌患者应用免疫组化SP法检测肿瘤组织ERCC1蛋白表达水平,所有患者一线给予SOX方案化疗最多6个周期,6个周期化疗后疾病无进展的患者随机分为两组：观察组（n=32）采取常规对症支持治疗,治疗组（n=28）在观察组基础上口服低剂量替吉奥胶囊80 mg/d,用药至患者无法耐受或者是疾病进展。结果 ERCC1蛋白表达阳性率为31.76%。ERCC1蛋白阳性表达组和阴性表达组化疗有效率分别为25.93%和63.79%（P〈0.05）。阳性组和阴性组中位肿瘤进展时间（m TTP）分别为4.5、6.0个月（P〈0.05）;阳性组和阴性组中位生存期（m OS）分别为10.7、14.6个月（P〈0.05）。治疗组和观察组m TTP分别为8.3、6.0个月（P〈0.05）。治疗组和观察组m OS分别为15.8、14.4个月（P=0.063）。治疗组白细胞减少、中性粒细胞减少及血小板减少发生率大于观察组（P〈0.05）,大多为Ⅰ～Ⅱ度,Ⅲ～Ⅳ度少见,治疗后均好转。结论晚期胃癌组织ERCC1蛋白表达水平能够预测一线SOX方案化疗疗效及患者预后。低剂量替吉奥胶囊维持治疗能够延长晚期胃癌患者一线化疗后肿瘤进展时间。

Objective To study the expression of ERCC1 in advanced gastric cancer （AGC） and its correlation with efficacy of first-line oxaliplatin-based chemotherapy and prognosis, and observe the survival and safety of low- dose S-1 maintenance chemotherapy after the first-line oxaliplatin-based chemotherapy. Methods Expression of ERCC1 protein in the tissues of 85 cases of initial treatment advanced gastric cancer was measured by immunohisto- chemistry （SP method）. Patients were treated with the combined chemotherapy of S-1 combined with oxaliplatin （SOX） 6 cycles at most. The patients who responded to the therapy were assigned to either the group with low - dose S-1 maintenance chemotherapy（ S-1 80 rag/d） or the observation group with follow-up. The maintenance ther- apy continued until disease progression or intolerable toxicity. Results The positive rate of ERCC1 protein was 31.76%. The response rates to chemotherapy in ERCC1 protein expression positive and negative group was 25.93% and 63.79% respeetively（P 〈0.05）. Median time to progression （mTYP） in the positive and negative group was 4.5 and 6.0 months respectively （ P 〈 0. 05 ）. The median overall survival （mOS） in the positive and negative group was 10.7 and 14.6 months respectively（P 〈 0. 05）. Median time to progression （mTYP） in the treatment group （ n = 28） and observation group （n = 32） was 8.3 and 6.0 months respectively （ P 〈 0. 05 ）. The median overall survival （mOS） in the treatment group and observation group was 15.8 and 14.4 months respectively （P = 0. 063）. The incidence rate of leuk-openia , neutropenia, thrombocytopenia in treatment group was higher than that in observation group（P 〈 0. 05）. Mostly Ⅰ - Ⅱ degrees, rare Ⅲ - Ⅳ degree, were improved after symp- tomatic treatment. Conclusion ERCC1 protein expression level in advanced gastric cancer tissue can predict the efficacy of first-line oxaliplatin-based chemotherapy and prognosisis of patients. Low-dose S-1 maintenance chemo- therapy can delay the tumor progression of patients with advanced gastric cancer after the first-line chemotherapy.