CAPOX方案相关肝损伤发生情况及其高危因素分析

Risk factors analysis of CAPOX-drug-induced liver injury

目的 总结Ⅱ~Ⅲ期结直肠癌患者根治术后接受卡培他滨联合奥沙利铂(CAPOX)方案化疗后药物性肝损伤的发生情况,并探索其非遗传高危因素.方法 收集来自中山大学肿瘤防治中心566例接受CAPOX方案辅助化疗的Ⅱ~Ⅲ期结直肠癌根治术后患者的人口学和临床特征.参考药物性肝损伤诊治指南评价药物性肝损伤,并对发生药物性肝损伤的患者进行分类;汇总发生药物性肝损伤的转归因素;使用Logistics回归分析筛选CAPOX方案导致的药物性肝损伤的非遗传高危因素.结果 55例(9.72%)患者被诊断为CAPOX导致的药物性肝损伤,其中89.09% 为肝细胞损伤型.绝大部分患者治疗转归良好.多因素分析显示年龄>51岁(OR=3.02,95%CI:2.132~4.831,P<0.001),合并使用抗肿瘤中成药(OR=1.771,95%CI:1.011~3.785,P=0.031)为高危因素;合并使用塞来昔布或阿司匹林(OR=0.454,95%CI:0.242~0.852,P=0.014)为肝损伤的保护因素.结论 Ⅱ~Ⅲ期结直肠癌患者根治术后接受CAPOX方案化疗后药物性肝损伤较常见,类型以肝细胞损伤型为主.年龄、合并使用抗肿瘤中成药是肝损伤的高危因素.

Objective To summarize drug-induced liver injury(DILI)situation and identify non-genetic risk factors for DILI among colorectal cancer patients receiving capecitabine plus oxaliplatin(CAPOX).Methods To collect the demographic and clinical characteristics of patients of stageⅡor stageⅢcolorectal cancer after curative resection who received CAPOX as adjuvant chemotherapy from Sun Yat-sen University Cancer Centre from 2010 January to 2013 June.566 patients’information were collected and analyzed.Diagnosis and classification of DILI were valued according to CIOMS standard.The outcome factors of drug-induced liver injury were summarized.Non-genetic risk factors for DILI among colorectal cancer patients treated with CAPOX were identified by logistic regression models.Results 55 patients(9.72%)were diagnosed as DILI caused by CAPOX,among which 89.09%were classified as hepatocellular type and were well cured.Multivariate analysis show that age>51(OR=3.02,95%CI:2.132~4.831,P<0.001),and concomitant with anti-tumor Chinese medicine(OR=1.771,95%CI:1.011~3.785,P=0.031)are the risk factors association with liver injury.However,concomitant with celecoxib or aspirin(OR=0.454,95%CI:0.242~0.852,P=0.014)is the protective factor.Conclusion CAPOX-drug-induced liver injury with a relatively high incidence should be addressed among stageⅡandⅢcolorectal cancer patients.DILI caused by CAPOX mainly manifested as hepatocellular type.Age and concomitant with anti-cancer Chinese medicine are high risk factors of DILI,which should be used as the potential predictors for DILI.