GEMOX方案联合免疫疗法对晚期胆管癌疗效及肿瘤标记物的影响

Clinical efficacy of GEMOX regimen combined with immunotherapy on advanced cholangiocarcinoma and its influence on tumor marker levels

目的探讨纳武利尤单抗联合GEMOX方案治疗晚期胆管癌的疗效及对肿瘤标记物的影响。方法选取2017年1月至2018年12月晚期胆管癌患者将100例通过随机数表法分为对照组和试验组,每组50例。对照组给予GEMOX方案治疗,吉西他滨,1000 mg/m 2,静脉滴注30 min,d1,8,奥沙利铂,100 mg/m 2,静脉滴注2 h,d1;试验组在对照组基础上,于化疗第1天,联合纳武利尤单抗治疗,240 mg静脉滴注,静脉滴注30 min,2周1次;2组均以21 d为1个周期,连续治疗4个周期。比较2组临床疗效、肿瘤标记物[癌胚抗原(CEA)、癌抗原(CA125)、糖类抗原(CA199、CA242、CA50)]的变化及毒副反应。结果治疗4个周期后,试验组和对照组客观缓解率(RR)分别为27.5%和18.00%,差异无统计学意义(P>0.05),试验组和对照组疾病控制率(DCR)分别为80.00%和58.00%,差异有统计学意义(P<0.05);治疗后,试验组和对照组CEA分别为(21.44±2.39)和(27.45±2.94)ng/ml,CA125分别为(43.05±2.60)和(52.25±5.62)kU/L,CA199分别为(248.34±35.57)和(312.22±46.08)kU/L,CA242分别为(23.57±1.88)和(31.50±2.78)U/ml,CA50分别为(30.40±3.59)和(46.09±3.43)μg/L,差异均有统计学意义(P<0.05);治疗期间,2组白细胞减少、血小板减少、血红蛋白减少、粒细胞减少、胃肠道反应、肾脏毒性、神经毒性、皮肤病变、骨髓抑制发生率比较,差异无统计学意义(P>0.05)。结论纳武利尤单抗联合GEMOX方案治疗晚期胆管癌可有效提高疾病控制率,降低肿瘤标志物的表达,且不增加不良反应。

Objective To study the curative efficacy of nivolumab combined with gemcitabine and oxaliplatin(GEMOX)regimen on advanced cholangiocarcinoma and its influence on tumor marker levels.Methods A total of 100 patients with advanced cholangiocarcinoma who were treated from January 2017 to December 2018 were recruited,and they were randomly divided into control group and treatment group,with 50 cases in each group.All patients were intervened with the GEMOX regimen,with gemcitabine,1,000mg/m 2,intravenous drip for 30min,d1 and 8+oxaliplatin,100mg/m^(2),intravenous drip for 2h,d1.Patinets in the treatment group were additionally treated with nivolumab,240mg intravenous drip for 30min,every 2 weeks.A total of 4 cycles,with 21d per cycle was performed.The clinical efficacy,tumor markers(carcinoembryonic antigen[CEA],carcinoembryonic antigen 125[CA125],carbohydrate antigens[CA199,CA242,CA50])and adverse events were compared between the two groups.Results After 4 cycles of treatment,there was no significant difference in the objective remission rate(RR)between the treatment group and control group(27.50%vs 18.00%,P>0.05).The disease control rate(DCR)in the treatment group was significantly higher than that in the control group(80.00%vs 58.00%,P<0.05).After treatment,CEA([21.44±2.39]ng/ml vs[27.45±2.94]ng/ml),CA125([43.05±2.60]kU/L vs[52.25±5.62]kU/L),CA199([248.34±35.57]kU/L vs[312.22±46.08]kU/L),CA242([23.57±1.88]U/ml vs[31.50±2.78]U/ml)and CA50([30.40±3.59]μg/L vs[46.09±3.43]μg/L)in the treatment group were significantly lower than those in the control group(all P<0.05).During the treatment,there was no significant difference in the incidence of leukopenia,thrombocytopenia,hemoglobin reduction,granulocytopenia,gastrointestinal reaction,nephrotoxicity,neurotoxicity,skin lesions,and myelosuppression between the two groups(P>0.05).Conclusion Nivolumab combined with the GEMOX regimen can effectively enhance the disease control rate of advanced cholangiocarcinoma,and reduce tumor marker levels without increasing the risk of adverse events.