【摘要】 目的观察以伊立替康为基础的二线化疗方案治疗晚期食管癌的安全性,同时探讨UGT1A1的基因多态性与伊立替康化疗安全性的关系。方法收集2012年5月至2015年2月期间在本科接受以伊立替康为基础的二线方案化疗的晚期食管癌患者42例,化疗前采集患者末梢血进行UGT1A1基因测序,观察化疗不良反应,分析UGT1A1基因多态性(UGT1A1*28和UGT1A1*6)与化疗不良反应的关系。结果 42例入选患者中,UGT1Al*28野生型(TA6/6)33例(78.6%),突变杂合型(TA6/7)7例(16.7%),突变纯合型(TA7/7)2例(4.8%);UGT1A1*6野生型(G/G)29例(69.0%),杂合突变型(G/A)11例(26.2%),纯合突变型(A/A)2例(4.8%)。主要不良反应为1~2度血液学毒性和胃肠道反应。UGT1A1*6突变型较野生型更容易发生3度以上中性粒细胞减少(6/13 vs 4/29,P<0.05);UGT1A1*28和UGT1A1*6的突变型较野生型发生腹泻的风险率均有所提高,但无统计学差异。结论以伊立替康为基础的二线化疗方案治疗晚期食管癌的安全性较高,UGT1A1*6多态性可以预测伊立替康的毒性反应。更多还原

【Abstract】 OBJECTIVE To observe the effects of irinotecan based second-line regimen in the treatment of advanced esophageal cancer,and discuss the correlation of UGT1A1 polymorphism and safety of irinotecan-based regimens treatment. METHODS A total of 42 advanced esophageal cancer patients received Irinotecan-based chemotherapy from February 2012 to May 2015. Peripheral blood of patients were collected for UGT1A1 gene sequencing before chemotherapy. And then the correlation of UGT1A1 polymorphism( UGT1A1* 28 and UGT1A1* 6) and adverse event of chemotherapy were analyzed. RESULTS The distribution of the genotypes in 42 advanced esophageal cancer patients was as followed: UGT1A1* 28 wild-type genotype TA6 /6( 33,78. 6%),heterozygous genotype TA6 /7( 7,16. 7%),and homozygous genotype TA7 /7( 2,4. 8%); UGT1A1 * 6 wild-type genotype GG( 29,69. 0%),heterozygous genotype GA( 11,26. 2%),and homozygous genotype AA( 2,4. 8%). The main adverse events were 1to 2 degrees of hematological toxicity and gastrointestinal reaction. The incidences of grade 3 and 4 neutropenia in the patients with UGT1A1 * 6 mutation type were higher than those in the wild-type genotype( 6 /13 vs. 4 /29,P <0. 05); the risk of diarrhea in the patients with UGT1A1 * 28 and UGT1A1 * 6 mutation type were slightly higher than those in the wild-type genotype,but no significant difference was statistically significant. CONCLUSION Irinotecan-based combination chemotherapy as second-line regimen is safe and well-tolerated in patients with advanced esophageal cancer. UGT1A1* 6 gene polymorphisms may predict adverse events of irinotecan.更多还原