CYP3A4*18基因多态性与初治晚期NSCLC患者EGFR-TKI疗效及不良反应的相关性分析
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篇名: CYP3A4*18基因多态性与初治晚期NSCLC患者EGFR-TKI疗效及不良反应的相关性分析
TITLE:
摘要: 目的:探讨细胞色素P450(CYP)3A4*18基因多态性与初治晚期非小细胞肺癌(NSCLC)患者表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)疗效及不良反应的相关性。方法:选取2013年1月-2016年3月于我院初次接受EGFR-TKI(吉非替尼或厄洛替尼)治疗至疾病进展或无法耐受的晚期NSCLC患者46例,采用聚合酶链反应及直接测序法检测各患者CYP3A4*18基因型,比较各基因型患者的临床疗效、无进展生存期(PFS)和不良反应发生情况。结果:46例患者中CYP3A4*18野生型17例,突变型29例,突变频率为63.0%。CYP3A4*18野生型患者的客观缓解率(ORR)为23.5%,疾病控制率(DCR)为70.6%;突变型患者的ORR为27.6%,DCR为69.0%;各基因型部分缓解、稳定、进展的患者比例以及ORR、DCR比较,差异均无统计学意义(P>0.05)。女性患者的PFS显著长于男性,无吸烟史者的PFS显著长于有吸烟史者,差异均有统计学意义(P<0.05);而患者的年龄、治疗药物、美国东部肿瘤协作组织评分、表皮生长因子受体(EGFR)突变类型、CYP3A4*18基因型等因素与其PFS无关(P>0.05);患者性别和吸烟史是PFS的独立预后因素[比值比分别为3.438、0.205,95%置信区间分别为(1.393,8.488)、(0.088,0.481)]。CYP3A4*18野生型患者发生皮疹的有6例(35.3%),腹泻的有3例(17.6%);突变型患者发生皮疹的有26例(89.7%),腹泻的有15例(51.7%),组间比较差异均有统计学意义(P<0.05);而各基因型患者肝功能损伤和间质性皮炎的发生率比较,差异均无统计学意义(P>0.05)。结论:CYP3A4*18基因多态性可能与初治晚期NSCLC患者EGFR-TKI的疗效无关,但与其不良反应的发生有关,突变型患者更有可能发生皮疹、腹泻等不良反应。
ABSTRACT: OBJECTIVE: To investigate the relationship of Cytochrome P450(CYP)3A4*18 gene polymorphism with therapeutic efficacy and ADR of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients receiving primary treatment. METHODS: A total of 46 advanced NSCLC patients receiving primary EGFR-TKI  (gefitinib or erlotinib) treatment until disease progression or intolerance were selected from our hospital during Jan. 2013-Mar. 2016, and (gefitinib of erlotinib) treatment until disease progression or intolerance. CYP3A4*18 genotype was detected by PCR and direct sequencing. Clinical efficacies, progression-free survival (PFS) and the occurrence of ADR were compared among different genotypes. RESULTS: Among 46 patients, there were 17 cases of CYP3A4*18 wild-type and 29 cases of CYP3A4*18 mutation-type, with mutation frequency of 63.0%. The objective response rate (ORR) of CYP3A4*18 wild-type patients was 23.5%, and disease control rate (DCR) of them was 70.6%. For CYP3A4*18 mutation-type patients, ORR and DCR were 27.6% and 69.0%. There was no statistical significance in the proportion of patients with partial response, stable disease or progressive disease, ORR or DCR among different genotypes (P>0.05). PFS of female patients were significantly longer than male patients; those of patients without smoking history were significantly longer than those with smoking history, with statistical significance (P<0.05). There was no correlation between patients’age, therapy drugs, Eastern Oncology Collaboration scores, EGFR mutation types, CYP3A4*18 genotypes and PFS (P>0.05). Patients’gender and smoking history were independent prognostic factors for PFS [odds ratios were 3.438, 0.205, 95% CI were(1.393,8.488),(0.088,0.481)]. Among CYP3A4*18 wild-type patients, 6 patients suffered from rash (35.3%) and 3 diarrhea (17.6%). Among mutation-type patients, 26 patients suffered from rash (89.7%) and 15 diarrhea (51.7%), with statistical significance (P<0.05). There was no statistical significance in the incidence of liver function injury and interstitial dermatitis among different genotypes (P>0.05). CONCLUSIONS: CYP3A4*18 gene polymorphism may be not associated with therapeutic efficacy of EGFR-TKI in advanced NSCLC patients receiving primary treatment, but it is correlated with the occurrence of ADR. Mutation type patients are more likely to suffered from rash, diarrhea and other ADR.
期刊: 2017年第28卷第32期
作者: 程艳芳,王艳娜,王慧,孟玲利,巩平
AUTHORS: CHENG Yanfang,WANG Yanna,WANG Hui,MENG Lingli,GONG Ping
关键字: CYP3A4*18基因;多态性;晚期非小细胞肺癌;表皮生长因子受体酪氨酸激酶抑制剂;疗效;不良反应;相关性
KEYWORDS: CYP3A4*18 gene; Polymorphism; Advanced non-small cell lung cancer; Epidermal growth factor receptor tyrosine kinase inhibitor; ADR; Relationship
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