目的:探讨检测 ERCC1 C8092A 在指导晚期食管癌患者个体化治疗中的作用及其意义。方法选取114例晚期食管癌患者入组,分为个体化治疗组(n =76)和标准治疗组(n =38)。标准治疗组采用顺铂联合紫杉醇化疗。采集随机入组到个体化治疗组患者外周血标本,均进行 ERCC1 C8092A 基因型的检测;如果基因型为非 C/ C 型,采用顺铂联合紫杉醇化疗(同标准治疗组),如果基因型为 C/ C 型,采用氟尿嘧啶联合紫杉醇化疗。主要观察指标包括缓解率,次要指标包括化疗毒副反应、无进展时间及总生存时间。两组间比较采用χ2检验。采用 Kaplan Meier 模型进行生存分析,生存率的比较采用 Log Rank 检验。结果个体化治疗组的缓解率为53.9%,标准治疗组缓解率为31.6%,两组差异有统计学意义(P 〈0.05)。个体化治疗组在化疗毒副反应中恶心呕吐(32.9%),血红蛋白减少(11.8%),Ⅲ-Ⅳ级发生率较标准治疗组(68.4%,28.9%)下降,两组差异有统计学意义(P 〈0.001,P =0.001)。个体化治疗组中位无疾病进展时间、总生存时间均优于标准治疗组,两组差异有统计学意义(P =0.004,P =0.007)。结论个体化治疗组的缓解率、化疗毒副反应、中位无进展时间及生存时间均优于标准治疗组,提示 ERCC1基因检测指导晚期食管癌个体化治疗可能具有一定临床价值。
Objective To explore the role and clinical values of detection of excision repair cross-complementing 1 (ERCC1) C8092A polymorphisms in individualized therapy of advanced esophageal cancer patients. Methods 114 advanced esophageal cancer patients were enrolled. Patients were randomly assigned to either the standard treatment group or the individualized treatment group. Patients in the standard treatment group received Paclitaxel plus cispla-tin. In the individualized treatment group,the ERCC1 C8092A polymorphisms were detected after DNA PCR ampli-fications,which extracted from peripheral blood karyocytes before the chemotherapies used. Patients with the AA or AC genotype of ERCC1 C8092A received Paclitaxel plus cisplatin,and those with CC genotype received Paclitaxel plus fluorouracil. The primary endpoints were response rate. The sencondary endpoints were toxicity of chemothera-py,progression freesurvival and overall survival. Differences between the groups were statistically analyzed by chi square test. Survival Differences were analyzed by Kaplan Meiersurvival curves. The survival rate was analyzed by Log Rank test. Results Response rate in the standard treatment group was 31. 6% . In the individualized treatment group was 53. 9% . There was statistically significant difference between two groups (P 〈 0. 05). The rates of gradeⅢ - Ⅳ nausea and vomitting (32. 9% ),anemia (11. 8% ) were significantly lower in individualized treatment group than in standard treatment group(68. 4% ,28. 9% ). There was statistically significant difference between the two groups (P 〈 0. 001,P = 0. 001). The media progression free survival time and overall survival time were signifi-cantly better in individualized treatment group than in standard treatment group (P = 0. 004,P = 0. 007). Conclu-sion The RR,toxicity of chemotherapy,PFS and OS are significantly better in individualized treatment group than in standard treatment group. Detection of ERCC1 gene polymorphism might be performed for advance