伊立替康不良反应影响因素的建模分析

发布时间：2018-04-03 19:00

本文选题：伊立替康　切入点：不良反应　出处：《山东大学》2014年硕士论文

【摘要】：目的：探讨伊立替康引起的重度不良反应的主要危险因素,并建立可预测各重度不良反应发生率的Logistic回归模型,评价各模型对相应重度不良反应的预测准确度。方法：回顾性分析自2011年9月-2013年9月入住山东大学齐鲁医院肿瘤内科并使用含伊立替康方案化疗的住院患者84例。密切监测患者化疗前及每周期化疗后常规血液学指标,以及每周期化疗后不良反应的发生情况,并根据药物不良反应常用术语标准CTCAE3.0版对不良反应进行分级；对每个纳入研究的患者采集3m1外周静脉血,检测患者UGT1A1*28与UGT1A1*6基因突变情况。详细记录每位患者年龄、性别、有无放疗、有无手术、是否四期、治疗前TBIL水平、治疗前HGB水平、UGT1A1*28基因型、UGT1A1*6基因型、转移灶数目、发病部位、KPS评分、化疗方案、既往化疗周期、剂量强度、体表面积等共16个可能影响伊立替康严重不良反应发生的因素。采用SPSS17.0软件对所有数据进行统计学处理,对这16个不良因素,分别与重度白细胞减少及首次使用伊立替康后发生重度白细胞减少、重度中性粒细胞减少及首次用药后重度中性粒细胞减少、重度迟发性腹泻及首次用药重度迟发性腹泻、重度呕吐及首次用药重度呕吐、胆碱能反应分别作单因素分析。通过初步单因素分析筛查后,取p0.8的因素变量作多因素Logistic回归分析,判断预测各因素是否与相应不良反应有关,并建立Logistic回归预测模型,采用ROC曲线分析评价其预测重度不良反应发生与否的准确度。结果：UGT1A1*28基因型、UGT1A1*6基因型和用药方案这三个因素进入重度白细胞减少的模型方程,预测正确率达到81.4%。UGT1A1*28、UGT1A1*6、既往化疗周期、治疗前HGB水平和发病部位(消化道或其他部位)这五个因素都进入了首次用药重度白细胞减少的模型中,预测正确率达到92.3%。UGT1A1*6和UGT1A1*28基因型、有无手术进入到重度中性粒细胞减少的模型方程,预测正确率达到77.1％.UGT1A1*28、UGT1A1*6和发病部位(消化道或其他部位)进入到首次用药重度中性粒细胞减少的模型方程,预测正确率达到75.5%。仅UGT1A1*6进入重度迟发性腹泻和首次用药后重度迟发性腹泻的模型中,预测正确率分别为69%和73.5%。性别与治疗前TBIL水平进入到胆碱能反应的模型方程,预测正确率达到78.1%。结论：对于使用含伊立替康方案化疗的患者,UGT1A1*28和UGT1A1*6的基因型对伊立替康所致重度白细胞减少和中性粒细胞减少的影响很关键,突变型比野生型更易发生重度血液毒性,且UGT1A1*6的纯合突变比杂合突变更易引起重度中性粒细胞减少。迟发性腹泻与UGT1A1*6基因型的关系更密切。治疗前TBIL15umol/L的女性更易发生胆碱能反应。
[Abstract]:Objective: to investigate the main risk factors of severe adverse reactions induced by Iriticogene, and to establish a Logistic regression model to predict the incidence of severe adverse reactions, and to evaluate the prediction accuracy of each model for the corresponding severe adverse reactions.Methods: from September 2011 to September 2013, 84 inpatients who were admitted to the Department of Oncology, Qilu Hospital, Shandong University and treated with Ilitecam regimen were analyzed retrospectively.The routine hematological indexes before and after chemotherapy and the occurrence of adverse reactions after chemotherapy were closely monitored, and the adverse reactions were classified according to the term standard CTCAE3.0.The peripheral venous blood of 3m1 was collected from each patient in the study, and the mutation of UGT1A1*28 and UGT1A1*6 gene was detected.Age, sex, radiotherapy, operation, stage 4, TBIL level before treatment, HGB level of UGT1A1O28 genotype, number of metastatic foci, site of disease score, chemotherapy regimen, previous chemotherapy cycle were recorded in detail.A total of 16 factors, such as dose intensity and body surface area, may affect the occurrence of severe adverse reactions of Ilitecam.All the data were statistically processed by SPSS17.0 software. The 16 adverse factors were associated with severe leukopenia and severe leukopenia after the first use of irinotecan, respectively.Severe neutropenia and severe neutropenia, severe delayed diarrhea, severe delayed diarrhea, severe vomiting, severe vomiting and cholinergic response were analyzed respectively.After screening by primary univariate analysis, the factor variables of p0.8 were used for multivariate Logistic regression analysis to determine whether the predicted factors were related to the corresponding adverse reactions, and the Logistic regression prediction model was established.ROC curve analysis was used to evaluate the accuracy of predicting the occurrence of severe adverse reactions.Results the three factors of the genetype: 1: UGT1A1O28 genotype and drug regimen entered the model equation of severe leukopenia, and the prediction accuracy rate was 81.4%. UGT1A1A1A1C6, the previous chemotherapy cycle.Before treatment, the HGB level and the location of the disease (digestive tract or other sites) were all included in the model of severe leukopenia for the first time, and the correct rate of prediction was 92.3%.UGT1A1*6 and UGT1A1*28 genotypes.The accuracy rate of prediction was 77.1. UGT1A1C28UGT1A1A1O6 and the diseased site (digestive tract or other parts) into the model equation of severe neutropenia for the first time. The prediction accuracy rate was 75.5%.Only UGT1A1*6 entered the model of severe delayed diarrhea and severe delayed diarrhea after the first medication, and the accuracy of prediction was 69% and 73.5%, respectively.Gender and TBIL level before treatment entered the model equation of cholinergic reaction, and the accuracy of prediction was 78.1%.Conclusion: the genotypes of UGT1A1O28 and UGT1A1*6 have a key effect on the severe leukopenia and neutropenia induced by Ilytecan regimen in patients with Ilitecam regimen, and the mutation type is more likely to develop severe hematotoxicity than the wild type.The homozygous mutation of UGT1A1*6 is more likely to cause severe neutropenia than heterozygous mutation.Delayed diarrhea was more closely associated with UGT1A1*6 genotypes.Women with TBIL15umol/L were more likely to develop cholinergic reactions before treatment.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R96

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