ERCC1蛋白检测指导晚期非小细胞肺癌个体化治疗的临床研究

doi:10.3969/j.issn.1007-3969.2013.05.002

中国癌症杂志 ›› 2013, Vol. 23 ›› Issue (5): 328-333.doi: 10.3969/j.issn.1007-3969.2013.05.002

ERCC1蛋白检测指导晚期非小细胞肺癌个体化治疗的临床研究

高志强¹,韩宝惠¹,沈策²,金先桥³,董竞成⁴,万欢英⁵,唐洁²,沈洁¹,顾爱琴¹,姜丽岩¹

1.上海交通大学附属胸科医院肺内科，上海 200030 ；
2.上海交通大学附属第六人民医院呼吸科，上海200233 ；
3.上海交通大学附属第一人民医院呼吸科，上海200080 ；
4.复旦大学附属华山医院中西医结合肺科，上海200040 ；
5.上海交通大学医学院附属瑞金医院呼吸科，上海200025

出版日期:2013-05-25 发布日期:2014-11-19
通信作者: 韩宝惠　E-mail:xkyyhan@gmail.com
基金资助:
上海市科委科技发展基金项目(No：06DZ19501)；上海市科委学科带头人计划项目(No：09XD1403500)

Clinical research of individualized therapy in advanced non-small cell lung cancer guiding by detection of ERCC1 protein

GAO Zhi-qiang, HAN Bao-hui, SHEN Ce, JIN Xian-qiao, DONG Jingcheng, WAN Huan-ying, TANG Jie, SHEN Jie, GU Ai-qin, JIANG Li-yan

1.Department of Pulmonary Medicine, Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, China; 2. Department of Pulmonary Medicine, No.6 People's Hospital Affiliated to Shanghai Jiao Tong University; Shanghai 200233, China; 3. Department of Pulmonary Medicine, No.1 People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200080, China; 4. Department of Integrated Traditional Chinese and Western Pulmonary Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China; 5.Department of Pulmonary Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Published:2013-05-25 Online:2014-11-19
Contact: HAN Bao-hui E-mail: xkyyhan@gmail.com

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摘要/Abstract

摘要：

背景与目的：核苷酸切除修复交叉互补组1(excision repair cross complementing 1，ERCC1)参与非小细胞肺癌(non-small cell lung cancer，NSCLC)铂类化疗药物的耐药发生。本研究旨在探讨ERCC1蛋白表达水平的检测在晚期NSCLC患者个体化治疗中的作用及其意义。方法：从2006年8月—2009年7月，共入组222例晚期(Ⅲ_B-Ⅳ期)NSCLC患者。采用免疫组化方法检测ERCC1蛋白在患者肺癌组织的表达。按2∶1的比例随机分为个体化治疗组(n=147)及标准治疗组(n=75)。标准治疗组采用含铂化疗方案健择/顺铂或诺维本/顺铂。个体化治疗组中ERCC1蛋白高表达的患者采用非铂化疗方案健择/诺维本，ERCC1蛋白低表达的患者采用健择/顺铂或诺维本/顺铂化疗方案。主要观察指标包括有效率、总生存期及疾病进展时间。两组间比较采用χ²检验。1年生存率和生存期的比较采用Life table和Kaplan-meier方法分析。结果：随访数据截至2012年9月30日。标准治疗组的有效率为26.6%，个体化治疗组为27.2%，两组差异无统计学意义(P=0.931)。标准治疗组的1年生存率为40.0%，个体化治疗组为48.3%，两组差异无统计学意义(χ²=1.379，P=0.24)。标准治疗组的中位生存时间为10.2个月(95%CI：8.67~11.73个月)，个体化治疗组为13.3月(95%CI：12.46~14.14个月)，两组差异有统计学意义(P=0.041)。标准治疗组的疾病进展时间为4.8个月(95%CI：4.12~5.48个月)，个体化治疗组的疾病进展时间为4.7个月(95%CI：3.88~5.52个月)，两组差异无统计学意义(P=0.395)。结论：个体化治疗组的中位生存时间较标准治疗组有所延长，但ERCC1蛋白的检测指导晚期NSCLC的个体化治疗并未体现出有效率、生存期及疾病进展时间方面的优势，分子指标的检测能否指导临床合理选择化疗方案有待于更深入的临床研究加以解决。

关键词: 癌, 非小细胞肺, 蛋白表达, 个体化治疗, 核苷酸切除修复交叉互补组

Abstract:

Background and purpose: Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. The study aimed to explore the role and clinical significance of detection of ERCC1 protein in individualized therapy of advanced non-small cell lung cancer (NSCLC) patients. Methods: From Aug. 2006 to Jul. 2009, 222 stage Ⅲ_B/Ⅳ NSCLC patients were enrolled. The expressions of ERCC1 protein in advanced stage NSCLC tissues were qualitatively detected by immunohistochemical methods. Patients were randomly assigned in a 2∶1 ratio to either the individualized treatment group or the standard treatment group before ERCC1 assessment. Patients in the control arm received gemcitabine plus cisplatin or vinorelbine plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received gemcitabine plus cisplatin or vinorelbine plus cisplatin, and those with high levels received gemcitabine plus vinorelbine. Main outcome measures include response rate, overall survival and time to progression. Differences between the groups were statistically analyzed by chi-square test. Survival differences were analyzed by temporal inspection and Kaplan-Meier survival curves. Results: Follow-up data was up to Sep. 30, 2012. Objective response was obtained by 20 patients (26.6%) in the standard treatment group and 40 patients (27.2%) in the individualized treatment group (P=0.931). One year survival rate was 40.0% in the standard treatment group and 48.3% in the genotypic arm (P=0.24). The median survival time was 10.2 months (95%CI was 8.67 months to 11.73 months) in the standard treatment group and 13.3 months (95%CI was 12.46 months to 14.14 months) in the individualized treatment group (P=0.041). The time to progression was 4.8 months (95%CI was 4.12 months to 5.48 months) in the standard treatment group and 4.7 months (95%CI was 3.88 months to 5.52 months) in the individualized treatment group (P=0.395). Conclusion: The median survival time has extended in the individualized treatment group. But individualized therapy in advanced NSCLC guiding by detection of ERCC1 protein has not reflected advantage in response rate, overall survival and time to progression. Additional studies are warranted to optimize detections of biomarkers in guiding rational clinical chemotherapy regimens.

Key words: Cancer, non-small cell lung, Protein expression, Individualized therapy, Excision repair crosscomplementing 1 (ERCC1)

高志强,韩宝惠,沈策,金先桥,董竞成,万欢英,唐洁,沈洁,顾爱琴,姜丽岩. ERCC1蛋白检测指导晚期非小细胞肺癌个体化治疗的临床研究[J]. 中国癌症杂志, 2013, 23(5): 328-333.

GAO Zhi-qiang, HAN Bao-hui, SHEN Ce, JIN Xian-qiao, DONG Jingcheng, WAN Huan-ying, TANG Jie, SHEN Jie, GU Ai-qin, JIANG Li-yan. Clinical research of individualized therapy in advanced non-small cell lung cancer guiding by detection of ERCC1 protein[J]. China Oncology, 2013, 23(5): 328-333.

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ERCC1蛋白检测指导晚期非小细胞肺癌个体化治疗的临床研究

Clinical research of individualized therapy in advanced non-small cell lung cancer guiding by detection of ERCC1 protein

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