CDA-G208A基因多态性对吉西他滨一线治疗肺鳞癌的疗效影响  

Effects of CDA-G208A gene polymorphism on the efficacy of gemcitabine in the first-line treatment of lung squamous cell carcinoma

作　　者：何杨 杨魁 栾家杰 HE Yang;YANG Kui;LUAN Jiajie(Department of Medical Oncology,the First Affiliated Hospital of Wannan Medical College,Wuhu 241001,Anhui,China;Department of Pharmacy,the First Affiliated Hospital of Wannan Medical College,Wuhu 241001,Anhui,China)

机构地区：[1]皖南医学院第一附属医院肿瘤内科,安徽芜湖241001 [2]皖南医学院第一附属医院药学部,安徽芜湖241001

出　　处：《中国临床药理学与治疗学》2023年第3期299-306,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：吴阶平医学基金会临床科研专项资助基金(No.320.6750.2020-04-10);皖南医学院校重点项目科研基金(WK2021ZF10)。

摘　　要：目的:探讨CDA-G208A基因多态性对吉西他滨一线治疗肺鳞癌疗效和安全性的影响。方法:回顾性筛选皖南医学院第一附属医院收治的局部晚期或转移性肺鳞癌患者65例,其中G208A基因GG型组(A组)纳入进行CDA-G208A基因检测结果为GG(野生纯合型)患者31例,G208A基因状态未知组(B组)纳入未行检测患者34例,两组患者均接受“吉西他滨+铂类”方案化疗至少2个周期。参照RECIST 1.1标准和NCI-CTC 5.0标准评估疗效和安全性。主要研究终点为无进展生存期(PFS)、总生存时间(OS)。次要研究终点包括客观有效率(ORR)、疾病控制率(DCR)、不良反应和PFS的影响因素。结果:A组和B组DCR为74.5%和50%(P=0.045);A组和B组m PFS分别为6.1个月和5.0个月(P=0.034);A组和B组m OS分别为13.3个月和12.0个月(P=0.388);A组和B组出现Ⅲ-Ⅳ级中性粒细胞减少病例数分别为2例和10例(P=0.017);多因素分析发现Ⅲ-Ⅳ级中性粒细胞减少是影响患者PFS的独立预后因素(P=0.045);G208A基因状态未知组发生Ⅲ-Ⅳ级中性粒细胞的可能更大(P=0.029)。绘制ROC表明CDA-G208A基因的多态性对化疗导致的中性粒细胞减少预测的AUC=0.756。结论:CDAG208A基因非GG型可以通过减慢吉西他滨在体内的代谢率,造成化疗后中性粒细胞减少,严重情况可间接降低吉西他滨的临床疗效。治疗前检测CDA-G208A基因状态对吉西他滨化疗导致的中性粒细胞减少具有一定的预测作用。AIM:To investigate the effect of CDAG208A gene polymorphism on the efficacy and safety of gemcitabine in the first-line treatment of lung squamous cell carcinoma.METHODS:Sixtyfive first-line treated patients with locally advanced or metastatic lung squamous cell carcinoma in The First Affiliated Hospital of Wannan Medical College hospital were screened.Group A included 31 patients tested with the GG(wild homozygous)CDAG208A gene,and group B included 34 patients without testing.All patients received gemcitabine plus platinum chemotherapy for at least 2 cycles.The efficacy and safety were evaluated following the RECIST 1.1 standard and the NCI-CTC 5.0 standard,respectively.The primary study endpoint was progression-free survival(PFS),overall survival(OS)and the secondary study endpoints included objective effective rate(ORR),disease control rate(DCR),adverse reactions,and influencing factors of PFS.RESULTS:The results showed that the DCR was 74.5%and 50%in group A and group B,respectively(P=0.045);mPFS was 6.1 months and 5.0 months in group A and group B,respectively(P=0.034);and the mOS was 13.3 months and 12.0 months in group A and group B,respectively,and there was no statistical difference(P=0.388).The number of cases of grade III-IV neutropenia in group A and group B was 2 and 10,respectively(P=0.017);grade III-IV neutropenia was an independent prognostic factor affecting patients with PFS(P=0.045);the group with unknown G208A gene status was more likely to develop grade III-IV neutrophils(P=0.029).The AUC of CDA-G208A gene predicting neutropenia caused by gemcitabine chemotherapy was 0.756.CONCLUSION:Non-GG type of CDAG208A gene can reduce the metabolic rate of gemcitabine in the body and cause neutropenia after chemotherapy.In severe cases,it can indirectly reduce the clinical efficacy of gemcitabine.The detection of CDA-G208A gene status before treatment can predict the neutropenia caused by gemcitabine chemotherapy.

关 键 词：CDA-G208A基因 吉西他滨 肺鳞癌 

分 类 号：R734[医药卫生—肿瘤]