帕博利珠单抗联合白蛋白紫杉醇与卡培他滨方案治疗进展期胃癌患者的疗效评估

Efficacy of pembrolizumab combined with albumin-bound paclitaxel and capecitabine in treatment of patients with advanced gastric cancer

目的探讨帕博利珠单抗联合白蛋白紫杉醇与卡培他滨方案在治疗进展期胃癌中的疗效。方法选取2019年10月至2022年9月西安交通大学附属红会医院收治的122例进展期胃癌患者进行随机对照试验,按照随机数字表法分为两组,各61例。对照组男48例、女13例,年龄(62.45±5.47)岁,接受卡培他滨方案联合白蛋白紫杉醇治疗;观察组男47例、女14例,年龄(63.14±5.65)岁,在对照组基础上增加帕博利珠单抗治疗。每3周为1个疗程,治疗2个疗程。对比两组患者临床疗效、治疗前后血清肿瘤标志物[糖类抗原724(CA-724)、糖类抗原199(CA-199)、血管内皮生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)]、不良反应及预后情况。采用t检验、χ^(2)检验。结果观察组总有效率为68.85%(42/61),高于对照组的47.54%(29/61),差异有统计学意义(χ^(2)=5.509,P=0.019)。治疗前,两组患者CA-724、CA-199、VEGF、TNF-α水平比较,差异均无统计学意义(均P>0.05);治疗6周后,观察组CA-724、CA-199、VEGF、TNF-α水平均低于对照组[(17.56±2.22)μg/L比(22.53±2.49)μg/L、(21.56±3.21)U/ml比(27.52±3.44)U/ml、(271.64±21.22)ng/L比(281.33±24.15)ng/L、(15.08±2.53)μg/L比(19.54±3.68)μg/L],差异均有统计学意义(t=11.636、9.893、2.354、7.800,均P<0.05)。观察组治疗期间Ⅲ~Ⅳ级血小板减少事件发生率为4.92%(3/61),低于对照组的18.03%(11/61),差异有统计学意义(χ^(2)=5.164,P=0.023);两组患者粒细胞减少、腹泻、甲状腺功能减退发生率比较,差异均无统计学意义(均P>0.05)。随访1年,观察组生存率为95.08%(58/61),高于对照组的83.61%(51/61),差异有统计学意义(χ^(2)=4.218,P=0.039)。结论帕博利珠单抗联合白蛋白紫杉醇治疗进展期胃癌的疗效良好,可有效降低血清肿瘤标志物水平。

Objective To explore the efficacy of pembrolizumab combined with albumin-bound paclitaxel in the treatment of patients with advanced gastric cancer.Methods From October 2019 to October 2022,122 patients with advanced gastric cancer treated at Hong hui Hospital,Xi'an Jiaotong University were selected for the randomized controlled trial,and were divided into an observation group and a control group by the random number table method,with 61 cases in each group.There were 47 males and 14 females in the observation group who were(63.14±5.65)years old.There were 48 males and 13 females in the control group who were(62.45±5.47)years old.The control group were treated with the capecitabine regimen and albumin-bound paclitaxel;in addition,the observation group took pembrolizumab.The clinical efficacies,serum levels of tumor markers[carbohydrate antigen-724(CA-724),carbohydrate antigen-199(CA-199),vascular endothelial growth factor(VEGF),and tumor necrosis factorα(TNFα)]before and after the treatment,and adverse reactions were compared between the groups using t andχ^(2) tests.Results The total effective rate in the observation group was higher than that in the control group[68.85%(42/61)vs.47.54%(29/61)],with a statistical difference(χ^(2)=5.509,P=0.019).Before the treatment,there were no statistical differences in the levels of CA-724,CA-199,VEGF,and TNFαbetween the two groups(all P>0.05).After the treatment,the levels of CA-724,CA-199,VEGF,and TNF-αin the observation group were lower than those in the control group[(17.56±2.22)μg/L vs.(22.53±2.49)μg/L,(21.56±3.21)U/ml vs.(27.52±3.44)U/ml,(271.64±21.22)ng/L vs.(281.33±24.15)ng/L,and(15.08±2.53)μg/L vs.(19.54±3.68)μg/L],with statistical differences(t=11.636,9.893,2.354,and 7.800;all P<0.05).The incidence of gradeⅢ-Ⅳthrombocytopenia in the observation group was lower than that in the control group[4.92%(3/61)vs.18.03%(11/61)],with a statistical difference(χ^(2)=5.164,P=0.023).There were no statistical differences in the incidences of neutropenia,diarrhea,and hypothyroidism between the two groups(all P>0.05).After one-year follow-up,the survival rate in the observation group was higher than that in the control group[95.08%(58/61)vs.83.61%(51/61)](χ^(2)=4.218,P=0.039).Conclusion The combination of pembrolizumab and albumin-bound paclitaxel for patients with advanced gastric cancer is effective,and can significantly reduce their levels of serum tumor markers.