分子标志物指导化疗药物选择的策略在晚期非小细胞肺癌化疗中的有效性及安全性评价

Evaluation of the efficacy and safety of the molecular markers-guided strategy of chemotherapy in advanced non-small cell lung cancer

背景与目的:切除修复交叉互补基因1(excision repair cross-complementation group 1,ERCC1)、核苷酸还原酶M1亚基(ribonucleotide reductase subunit M1,RRM1)等分子标志物已发现和化疗药物的疗效密切相关,并有可能成为预测疗效以及指导治疗的重要因素。本研究旨在进一步评价分子标志物指导化疗药物选择的策略在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者治疗中的有效性及安全性。方法:73例Ⅲ或Ⅳ期NSCLC患者根据病理组织充足与否,分为免疫组化指导治疗组(A组)及对照组(B组),A组使用免疫组化方法检测ERCC1、RRM1以及Ⅲ型β微管蛋白,并根据分子标志物指导化疗药物的选择。B组则使用吉西他滨+顺铂治疗。结果:A组治疗总有效率明显高于B组(57.9%vs 34.3%,P=0.043)。A组及B组中位无进展生存时间分别为156 d和126 d,差异有统计学意义(P=0.000);中位生存时间分别为385 d和354 d;生存总时间差异无统计学意义(P=0.127)。A组及B组1年生存率、Ⅲ级以上化疗不良反应及化疗前后PS评分改善率差异均无统计学意义(P>0.05)。A组中吉西他滨+顺铂方案治疗有效率明显高于B组(71.4%vs 34.3%,P=0.018)。结论:免疫组化检测分子标志物指导化疗的策略能够提高化疗有效率,延长疾病无进展生存时间。吉西他滨+顺铂方案在分子标志物指导化疗药物选择的策略下应用,将取得更高的治疗缓解率。

Background and purpose：It has been found that ERCC1,RRM1 and other molecular markers is closely related to the efficacy of chemotherapy,and may become an important factor in guiding chemotherapy and predicting efficacy.This study aimed to evaluate the efficacy and safety of the molecular markers-guided strategy of chemotherapy in advanced non-small cell lung cancer（NSCLC）.Methods：According to the condition of tumor specimen,73 patients with NSCLC（stageⅢor stageⅣ）were divided into 2 groups：the molecular markers-guided group（Group A）and the control group（Group B）.The expression of ERCC 1,RRM1 andβ-tubulin-Ⅲwere detected with immunohistochemical methods in tumor specimens obtained from Group A.Patients of Group A received chemotherapy based on the molecular markers-guided strategy.Patients of Group B received chemotherapy of gemcitabin＋cisplatin.Results：There was significant difference between Group A and Group B in response rate（57.9% vs 34.3%,P=0.043）.Median survival time of Group A and Group B were 337 and 367 days,median time-to-progression of Group A and Group B were 124 and 140 days.There was significant difference between Group A and Group B in progression-free survival（p=0.000）,but no obvious difference in overall survival（P=0.127）.One year survival rate,the improvement rate of PS and over gradeⅢtoxicity of chemotherapy were similar in Group A and Group B.Response rates of Group A patients who received GP were obviously higher than those of Group B（71.4%vs 34.3%,p=0.018）. Conclusion：The molecular markers-guided strategy improves response rate of chemotherapy and the progression-free survival of patients,especially when GP was selected by the strategy.