GEMOX方案联合靶向药物治疗晚期胆囊癌的临床疗效

Clinical efficacy of GEMOX regimen combined with targeted therapy for advanced gallbladder cancer

目的评价GEMOX(吉西他滨+奥沙利铂)方案联合靶向药物治疗晚期胆囊癌的临床疗效.方法采用回顾性描述性研究方法.收集2016年1月至2017年12月上海交通大学医学院附属新华医院收治的21例晚期胆囊癌患者的临床资料;男8例,女13例;年龄为(58±12)岁,年龄范围为28~80岁.患者行GEMOX方案联合靶向药物治疗,根据基因检测结果选取西妥昔单克隆抗体、曲妥珠单克隆抗体和阿帕替尼靶向药物治疗.观察指标:(1)基因检测情况.(2)GEMOX方案联合靶向药物治疗情况.(3)GEMOX方案联合靶向药物治疗的不良反应情况.正态分布的计量资料以Mean±SD表示,偏态分布的计量资料以M(范围)表示.计数资料以绝对数或百分比表示.采用Kaplan-Meier法绘制生存曲线并计算生存率,采用Log-rank检验进行生存分析.结果(1)基因检测情况:21例患者中,K-ras野生型19例[单纯K-ras野生型13例、K-ras野生型合并人类表皮生长因子受体2(HER2)阳性4例、合并血管内皮生长因子受体2(VEGFR2)阳性2例],HER2阳性5例(单纯HER2阳性1例、HER2阳性合并K-ras野生型4例),VEGFR2阳性3例(单纯VEGFR2阳性1例、VEGFR2阳性合并K-ras野生型2例).美国东部肿瘤协作组(ECOG)评分为0分2例,评分为1分19例.(2)GEMOX方案联合靶向药物治疗情况:21例患者均完成≥2个疗程的GEMOX方案联合靶向药物治疗,其完全缓解(CR)、部分缓解(PR)、疾病稳定(SD)、疾病进展(PD)分别为O、4、9、8例.14例(单纯K-ras野生型13例、K-ras野生型合并VEGFR2阳性1例)患者GEMOX方案联合西妥昔单克隆抗体治疗,其CR、PR、SD、PD分别为0、4、5、5例;5例(单纯HER2阳性1例、HER2阳性合并K-ras野生型4例)联合曲妥珠单克隆抗体治疗,其CR、PR、SD、PD分别为0、0、2、3例;2例(单纯VEGFR2阳性1例、合并K-ras野生型1例)联合阿帕替尼治疗,其CR、PR、SD、PD分别为0、0、2、0例.21例患者客观有效率为19.0%(4/21),疾病控制率为61.9%(13/21).21例患者中位起效时间为1.8个月.21例患者3、6、9个月无疾病进展生存率分别为90.5%、71.4%、58.5%,中位无疾病进展生存时间(PFS)为10.7个月.21例患者6、12个月总生存率分别为90.2%、58.6%,中位总生存时间(OS)为15.5个月.7例合并有黄疸的晚期胆囊癌患者PFS和OS分别为8.4个月和10.4个月,14例无黄疸的晚期胆囊癌患者上述指标分别为10.5个月和14.8个月,两者PFS和OS比较,差异无统计学意义(x2=0.868,0.774,P>0.05).(3)GEMOX方案联合靶向药物治疗的不良反应情况:主要不良反应包括皮肤病变及消化道反应,无严重不良反应.不良反应经对症治疗后均缓解.结论GEMOX方案联合靶向药物治疗晚期胆囊癌患者效果良好,不良反应小,安全性较高.

Objective To evaluate the clinical efficacy of gemcitabine-oxaliplatin (GEMOX)regimen combined with targeted therapy for advanced gallbladder cancer.Methods The retrospective descriptive study was conducted.The clinical data of 21 patients with advanced gallbladder cancer who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between January 2016 and December 2017were collected,including 8 males and 13 females,aged from 28 to 80 years,with the age of (58_+12)years. Patients received GEMOX regimen combined with targeted therapy.According to the results of gene test,patients selected tageted therapy with Cetuximab,Hereeptin or Apatinib.Observation indicators :(1)gene test situations;(2)situations of GEMOX regimen combined with targeted therapy;(3)adverse reactions of GEMOX regimen combined with targeted therapy.Measurement data with normal distribution were represented as Mean±SD,and measurement data with skewed distribution were described as M (range).Count data were represented as absolute number or percentage.The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method.The survival analysis was done using the Log-rank test.Results (1)Gene test situations:of 21 patients,19 were confirmed as K-ras wild type,including 13 of single K-ras wild type,4 of K-ras wild type combined with human epidermal growth factor receptor 2 (HER2),2 of K-ras wild type combined with vascular endothelial growth factor receptor 2 (VEGFR2);5 were detected positive HER2,including 1 of single positive HER2,4 of positive HER2 combined with K-ras wild type;3 were detected positive VEGFR2,including 1 of single positive VEGFR2,2 of positive VEGFR2 combined with K-ras wild type.Two and 19 patients had 0 and 1 of Eastern Cooperative Ontology Group score.(2)Situations of GEMOX regimen combined with targeted therapy: all the 21 patients underwent I>2 courses of GEMOX regimen combined with targeted therapy.Among the 21 patients,0,4,9 and 8 were respectively detected in the complete remission (CR),partial remission (PR), stable disease (SD)and disease progression (PD).Fourteen patients (13 of single K-ras wild type and 1 of K-ras wild type combined with positive VEGFR2)received GEMOX regimen combined with Cetuximab therapy, including 0 with CR,4 with PR,5 with SD and 5 with PD;5 patients (1 of single positive HER2 and 4 of positive HER2 combined with K-ras wild type)received GEMOX regimen combined with Herceptin therapy,including 0 with CR,0 with PR,2 with SD and 3 with PD;2 patients (1 of single positive VEGFR2 and 1 of positive VEGFR2 combined with K-ras wild type)received GEMOX regimen combined with Apatinib therapy,including 0 with CR,0 with PR,2 with SD and 0 with PD.The objective response rate was 19.0%(4/21)and disease control rate was 61.9%(13/21)in the 21 patients.The median onset time was 1.8 months in the 21 patients.The 3-,6- and 9-month progression free survival (PFS)rates and median PFS time were respectively 90.5%,71.4%, 58.5%and 10.7 months.The 6-and 12-month overa/2 survival rates were respectively 90.2%and 58.6%,and median overall survival (OS)time was 15.5 months in the 21 patients.The PFS and OS time were 8.4 months and 10.4 months in the 7 patients combined with jaundice,10.5 months and 14.8 months in the 14 patients without jaundice,with no statistically significant difference (X^2 =0.868,0.774,P>0.05).(3)Adverse reactions of GEMOX regimen combined with targeted therapy:the most common adverse events were skin rash and digestive tract reactions.No serious adverse event occurred during the therapy.All the adverse events were improved after symptomatic treatments.Conclusion GEMOX regimen combined with targeted therapy for advanced gallbladder cancer has good outcomes,less adverse reactions and higher safety.