UTG1A128基因型指导伊立替康用药剂量选择的回顾性分析

Retrospective analysis on the dosage of Irinotecan guided by UTG1A1*28 genotype

目的研究UTG1A1＊28的不同基因型结直肠癌患者应用伊立替康后严重不良反应发生率与用药剂量的关系。方法回顾性分析2012-08-01-2014-03-31郑州大学第一附属医院111例结直肠癌患者UTG1A1＊28基因多态性情况,记录伊立替康用药剂量,分析不同基因型患者应用伊立替康后严重不良反应发生率与用药剂量的关系。结果111例采用含伊立替康方案化疗的结直肠癌患者中,TA6/6、TA6/7和TA7/7各基因型分别有85、26和0例。85例TA6/6型患者应用低剂量伊立替康（每周50-79 mg/m^2）36例,中等剂量（每周80-99 mg/m^2）38例,高剂量（每周100-120mg/m^2）11例;发生3级以上腹泻分别为7例（19.44%）、8例（21.05%）和3例（27.27%）,发生3级以上中性粒细胞减少分别为4例（11.11%）、4例（10.52%）和2例（18.18%）;组间对比差异均无统计学意义（3级以上腹泻P=0.856,3级以上中性粒细胞减少P=0.645）。26例T6/7型患者低剂量组9例,中等剂量组11例,高剂量组6例;3组发生3级以上腹泻分别为2（22.22%）例、2例（18.18%）和5例（83.33%）,发生3级以上中性粒细胞减少分别为1例（11.11%）、2例（18.18%）和2例（33.33%）;高剂量组3级以上腹泻发生率显著高于中、低剂量组,P=0.011;而3级以上中性粒细胞减少发生率差异无统计学意义,P=0.305。结论对于应用伊立替康的患者推荐检测UGT1A1＊28基因来指导个体化治疗。应用伊立替康不良反应发生率低,对于TA6/6型患者,可考虑适当增加伊立替康剂量以提高疗效。

OBJECTIVE To observe the relation between the incidence of adverse reaction and the drug dosage after the application of Irinotecan to different UGT1A1＊28genetic patients with colorectal cancer.METHODS This study retrospectively counted the UGT1A1＊28genetic polymorphism of 111 patients with colorectal cancer from August 1st2012 to March 31 st 2014,and recorded the adverse reaction during chemotherapy and the dosage of Irinotecan to analyze the relation between the incidence of adverse reaction and the drug dosage after the application of Irinotecan to different UGT1A1＊28genetic patients.RESULTS Among 111 patients with colorectal cancer treated by the chemotherapy containing Irinotecan,85 cases（76.58%）were identified in people with TA6/6 genotype,compared with 26 cases（23.42%）in TA6/7genotype and 0cases in TA7/7genotype.Among 85 patients with TA6/6genotype,36 cases were treated with Irinotecan in low-dose,38 cases in medium-dose（80-90 mg/m^2,every week）and 11 cases in high-dose（100-120mg/m^2,every week）.7cases（19.44%）,8cases（21.05%）,3cases（27.27%）had grade 3-5diarrhea and4cases（11.11%）,4cases（10.52%）,2cases（18.18%）had grade 3-5neutropenia respectively.No significant difference was found in these three groups（grade 3-5diarrhea P=0.856,grade 3-5neutropenia P=0.645）.Among 26 patients with TA6/7genotype,there were 9cases in low-dose group,11 cases in medium-dose group and 6cases in high-dose group.2cases（22.22%）,2cases（18.18%）,5cases（83.33%）had grade 3-5diarrhea and 1cases（11.11%）,2cases（18.18%）,2cases（33.33%）had grade 3-5neutropenia respectively.The high-dose group showed higher incidence of grade 3-5diarrhea compared with the medium-dose group（P=0.011）,while the three groups had similar incidence of grade 3-5neutropenia（P=0.305）.CONCLUSIONS For the patients treated by Irinotecan.we should detect the genotypes of UGT1A1＊28to guide individual treatment.For patients with TA6/6genotype,the dosage of irinotecan can be increased in order to improve the efficacy.