本文選題：伊立替康　切入點(diǎn)：不良反應(yīng)　出處：《山東大學(xué)》2014年碩士論文

【摘要】：目的：探討伊立替康引起的重度不良反應(yīng)的主要危險(xiǎn)因素,并建立可預(yù)測(cè)各重度不良反應(yīng)發(fā)生率的Logistic回歸模型,評(píng)價(jià)各模型對(duì)相應(yīng)重度不良反應(yīng)的預(yù)測(cè)準(zhǔn)確度。 方法：回顧性分析自2011年9月-2013年9月入住山東大學(xué)齊魯醫(yī)院腫瘤內(nèi)科并使用含伊立替康方案化療的住院患者84例。密切監(jiān)測(cè)患者化療前及每周期化療后常規(guī)血液學(xué)指標(biāo),以及每周期化療后不良反應(yīng)的發(fā)生情況,并根據(jù)藥物不良反應(yīng)常用術(shù)語(yǔ)標(biāo)準(zhǔn)CTCAE3.0版對(duì)不良反應(yīng)進(jìn)行分級(jí)；對(duì)每個(gè)納入研究的患者采集3m1外周靜脈血,檢測(cè)患者UGT1A1*28與UGT1A1*6基因突變情況。詳細(xì)記錄每位患者年齡、性別、有無(wú)放療、有無(wú)手術(shù)、是否四期、治療前TBIL水平、治療前HGB水平、UGT1A1*28基因型、UGT1A1*6基因型、轉(zhuǎn)移灶數(shù)目、發(fā)病部位、KPS評(píng)分、化療方案、既往化療周期、劑量強(qiáng)度、體表面積等共16個(gè)可能影響伊立替康嚴(yán)重不良反應(yīng)發(fā)生的因素。采用SPSS17.0軟件對(duì)所有數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)處理,對(duì)這16個(gè)不良因素,分別與重度白細(xì)胞減少及首次使用伊立替康后發(fā)生重度白細(xì)胞減少、重度中性粒細(xì)胞減少及首次用藥后重度中性粒細(xì)胞減少、重度遲發(fā)性腹瀉及首次用藥重度遲發(fā)性腹瀉、重度嘔吐及首次用藥重度嘔吐、膽堿能反應(yīng)分別作單因素分析。通過(guò)初步單因素分析篩查后,取p0.8的因素變量作多因素Logistic回歸分析,判斷預(yù)測(cè)各因素是否與相應(yīng)不良反應(yīng)有關(guān),并建立Logistic回歸預(yù)測(cè)模型,采用ROC曲線分析評(píng)價(jià)其預(yù)測(cè)重度不良反應(yīng)發(fā)生與否的準(zhǔn)確度。 結(jié)果：UGT1A1*28基因型、UGT1A1*6基因型和用藥方案這三個(gè)因素進(jìn)入重度白細(xì)胞減少的模型方程,預(yù)測(cè)正確率達(dá)到81.4%。UGT1A1*28、UGT1A1*6、既往化療周期、治療前HGB水平和發(fā)病部位(消化道或其他部位)這五個(gè)因素都進(jìn)入了首次用藥重度白細(xì)胞減少的模型中,預(yù)測(cè)正確率達(dá)到92.3%。UGT1A1*6和UGT1A1*28基因型、有無(wú)手術(shù)進(jìn)入到重度中性粒細(xì)胞減少的模型方程,預(yù)測(cè)正確率達(dá)到77.1％.UGT1A1*28、UGT1A1*6和發(fā)病部位(消化道或其他部位)進(jìn)入到首次用藥重度中性粒細(xì)胞減少的模型方程,預(yù)測(cè)正確率達(dá)到75.5%。僅UGT1A1*6進(jìn)入重度遲發(fā)性腹瀉和首次用藥后重度遲發(fā)性腹瀉的模型中,預(yù)測(cè)正確率分別為69%和73.5%。性別與治療前TBIL水平進(jìn)入到膽堿能反應(yīng)的模型方程,預(yù)測(cè)正確率達(dá)到78.1%。 結(jié)論：對(duì)于使用含伊立替康方案化療的患者,UGT1A1*28和UGT1A1*6的基因型對(duì)伊立替康所致重度白細(xì)胞減少和中性粒細(xì)胞減少的影響很關(guān)鍵,突變型比野生型更易發(fā)生重度血液毒性,且UGT1A1*6的純合突變比雜合突變更易引起重度中性粒細(xì)胞減少。遲發(fā)性腹瀉與UGT1A1*6基因型的關(guān)系更密切。治療前TBIL15umol/L的女性更易發(fā)生膽堿能反應(yīng)。
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R96

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本文編號(hào)：1706495