CYP3A5*3基因多态性与晚期非小细胞肺癌患者应用多西他赛的疗效及安全性分析

目的:研究CYP3A5*3基因多态性对应用多西他赛治疗的晚期非小细胞肺癌患者的疗效以及安全性的相关性分析。方法:通过多基因检测技术明确患者CYP3A5*3的基因多态性状态,通过查阅随访表、病理以及随访电话明确患者的基本信息,包括性别、年龄、是否吸烟、EGFR状态和ECOG评分等,明确生存信息,即无进展生存期(PFS)和总生存期(OS)。通过不良反应表统计不良反应发生情况。用卡方检验对基因多态性与患者的不良反应进行相关性分析,用Kaplan-Meier生存曲线分析基因多态性与患者的PFS和OS的关系。结果:在生存分析方面,CYP3A5*3纯合突变型患者的中位总生存期约26个月,高于杂合型的24个月和野生型的22个月(P=0.833)。CYP3A5*3纯合突变型患者的中位无进展生存期4个月,也高于杂合型的2个月和野生型的3个月(P=0.306)。在不良反应方面,共有11例患者发生Ⅲ级以上骨髓抑制,其中7例(63.6%)患者为CYP3A5*3纯合突变型,考虑该基因型发生中重度骨髓抑制的可能性更大(P=0.415)。此外,有6例患者发生皮疹,其中5例(83.3%)为CYP3A5*3纯合突变型,还包括1例Ⅲ度皮疹。考虑该基因型患者发生皮疹的可能性更大(P=0.490)。手足综合征、神经毒性、肾毒性以及口腔黏膜炎等仅发生在CYP3A5*3野生型及CYP3A5*3纯合突变型患者中。结论:应用多西他赛的晚期非小细胞肺癌患者中,CYP3A5*3纯合突变型患者的生存期高于杂合型和野生型患者。CYP3A5*3纯合突变型患者发生中重度骨髓抑制、皮疹的风险可能性更大。

Analysis of the efficacy and safety of CYP3A5*3 genetic polymorphisms in patients with advanced non-small cell lung cancer treated with docetaxel

Objective:The CYP450 family has a wide range of genetic polymorphisms.There are many CYP3A5 *3 genetic polymorphisms in Chinese population.This study focuses on the efficacy and safety of this gene polymorphisms in patients with advanced non-small cell lung cancer treated with docetaxel.Methods:The polymorphisms of CYP3A5*3 was identified by multi-gene detection technology.The basic information of the patients，including gender，age，smoking history，EGFR status and ECOG score，were identified by reviewing the follow-up table，pathology and follow-up telephone.The survival information，including progression-free survival (PFS) and overall survival (OS) was identified.The occurrence of adverse reactions was counted by the adverse reaction table.Correlation analysis between genetic polymorphisms and adverse reactions was performed by chi-square test.The Kaplan-Meier survival curve was used to analyze the relationship between gene polymorphism and PFS and OS of patients.Results:In terms of survival analysis，the median overall survival of patients with CYP3A5*3 homozygous mutant type was approximately 26 months，higher than the heterozygous 24 months and the wild type 22 months (P=0.833).The median progression-free survival (4 months) was also higher in patients with CYP3A5*3 homozygous mutant type than in heterozygous (2 months) and wild-type (3 months) patients (P=0.306).In terms of adverse reactions，a total of 11 patients developed grade Ⅲ or higher myelosuppression，of which 7 (63.6%) patients were homozygous for CYP3A5*3，and it is more likely that this genotype will have moderate to severe myelosuppression (P=0.415).In addition，there were 6 patients with rash，and 5(83.3%) were CYP3A5*3 homozygous mutant type，including 1 case with Ⅲ degree rash，considering this genotype was more likely to develop skin rash (P=0.490).Hand-foot syndrome，neurotoxicity，nephrotoxicity，and oral mucositis occurred only in patients with CYP3A5*3 wild type and CYP3A5*3 homozygous mutant type.Conclusion:In patients with advanced non-small cell lung cancer treated with docetaxel，the patients with CYP3A5*3 homozygous mutations have higher survival than heterozygous and wild-type patients.The patients with CYP3A5*3 homozygous mutations are more likely to have moderate to severe myelosuppression and skin rash.