阿帕替尼联合卡瑞利珠治疗对晚期食管鳞癌患者SCC-Ag、CYFRA21-1因子的影响

The effect of apartinib combined with carilizhu on SCC-Ag and CYFRA21-1 factors in patients with advanced esophageal squamous cell carcinoma

目的探讨阿帕替尼联合卡瑞利珠治疗对晚期食管鳞癌患者鳞状细胞癌抗原(SCC-Ag)、细胞角蛋白19片段(CYFRA21-1)因子的影响。方法前瞻性纳入2018年1月至2020年2月在阜阳市第二人民医院治疗80例晚期食管鳞癌患者作为研究对象,根据患者选择治疗方案的不同将分为研究组41例和对照组39例。对照组给予吉西他滨(第1至8天,1000 mg/m^(2),静脉滴注)联合顺铂(第1~3天,25 mg/m^(2),静脉滴注)治疗,21 d为一个周期。研究组应用阿帕替尼(第1~18天,250 mg,口服)联合卡瑞利珠(第18天后,200 mg,静脉滴注,1次/2周)进行治疗,直至患者不可耐受或退出研究。分析与比较2组患者临床疗效差异,血清中肿瘤标志物[癌胚抗原(CEA)、糖类抗原(CA125)]及SCC-Ag、CYFRA21-1水平变化,统计生活质量、治疗期间不良反应、远期生存情况。结果研究组客观缓解率(35.90%)、疾病控制率(87.18%)均显著高于对照组(10.26%、53.85%),差异均有统计学意义(P<0.05)。治疗1个月后,研究组患者的CEA、CA125、SCC-Ag、CYFRA21-1水平分别为(14.49±3.43)ng/mL、(70.23±13.41)U/mL、(6.28±1.63)μg/mL、(29.58±9.12)ng/mL,明显低于对照组[(23.57±4.73)ng/mL、(90.73±16.54)U/mL、(8.92±1.77)μg/mL、(36.22±8.15)ng/mL],差异均有统计学意义(P<0.05)。研究组患者发生Ⅰ~Ⅱ级腹泻、恶心呕吐、白细胞下降及血小板下降等不良反应发生率(28.21%、2.56%、20.51%、7.69%)均明显低于对照组(61.54%、20.51%、38.46%、28.21%),差异均有统计学意义(P<0.05),2组患者在肝功能异常和红细胞下降方面差异无统计意义(P>0.05)。研究组Ⅲ~Ⅳ度白细胞下降发生率(5.13%)显著低于对照组(28.21%),差异有统计学意义(P<0.05),Ⅲ~Ⅳ度红细胞下降发生率分别为5.13%和2.56%,差异无统计意义(P>0.05)。研究组患者的KPS评分提升率(97.44%)显著高于对照组(74.35%),差异有统计学意义(P<0.05)。研究组的无进展生存期(8.43个月)较对照组(6.73个月)显著延长,差异有统计学意义(P<0.05)。结论与吉西他滨联合顺铂方案相比,阿帕替尼联合卡瑞利珠治疗晚期食管鳞癌患者疗效更佳,可显著降低患者血清SCC-Ag、CYFRA21-1水平,提高患者的生活质量,延长患者的生存时间,且安全性较好,值得临床推广。

Objective To investigate the effect of apartinib combined with Karelia bead therapy on the expression of squamous cell carcinoma antigen(SCC-Ag)and cytokeratin 19 fragment(CYFRA21-1)in advanced esophageal squamous cell carcinoma(ESCC).Methods A total of 80 patients who were treated with advanced esophageal squamous cell carcinoma in Fuyang Second People's Hospital from January 2018 to February 2020 were prospectively included in the study.They were divided into a study group 41 cases and a control group 39 cases according to the treatment options selected by the patients.The control group was treated with gemcitabine(on days 1 to 8,1000 mg/m^(2),intravenous drip)combined with cisplatin(on days 1 to 3,25 mg/m^(2),intravenous drip),with 21 days as a cycle,and the research group was treated with apatinib(on days 1 to 18,250 mg,oral administration)combined with carleilizhu(on day 18,200mg,intravenous drip,1 time/2 weeks)until the patient could not tolerate or withdrew from the study.The clinical efficacy difference between the two groups of patients,the serum tumor markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA125)],SCC-Ag,CYFRA21-1 level were analyzed and compared,quality of life,adverse reactions during the treatment,the long-term survival situation was counted.Results The objective response rate(35.90%)and disease control rate(87.18%)of the study group were significantly higher than those of the control group(10.26%,53.85%),and the differences were statistically significant(P<0.05).After 1 month of treatment,the levels of CEA,CA125,SCC-Ag,and CYFRA21-1 in the study group were(14.49±3.43)ng/mL,(70.23±13.41)U/mL,(6.28±1.63)μg/mL,(29.58±9.12)ng/mL,respectively,which were significantly lower than those in the control group[(23.57±4.73)ng/mL,(90.73±16.54)U/mL,(8.92±1.77)μg/mL,(36.22±8.15)ng/mL],and the differences were statistically significant(P<0.05).The incidence of adverse reactions in the study group(28.21%,2.56%,20.51%,7.69%)such as grade Ⅰ~Ⅱ diarrhea,nausea and vomiting,leukopenia,and thrombocytopenia were significantly lower than those in the control group(61.54%,20.51%,38.46%,28.21%),the differences were statistically significant(P<0.05).There was no statistically significant difference in liver function abnormalities and red blood cell decline between the 2 groups(P>0.05).The incidence of Ⅲ~Ⅳ degree leukopenia in the study group(5.13%)was significantly lower than that of the control group(28.21%),and the difference was statistically significant(P<0.05).The incidence of Ⅲ~Ⅳ degree red blood cell decline was 5.13% and 2.56%,respectively,there was no statistically significant difference(P>0.05).The improvement rate of KPS score in the study group(97.44%)was significantly higher than that in the control group(74.35%),and the difference was statistically significant(P<0.05).The progression-free survival of the study group(8.43 months)was significantly longer than that of the control group(6.73 months),the difference was statistically significant(P<0.05).Conclusion Compared with gemcitabine combined with cisplatin,apatinib combined with Carrelizol has a better effect in the treatment of patients with advanced esophageal squamous cell carcinoma.It can significantly reduce the patient's serum SCC-Ag and CYFRA21-1 levels,improve patient survival time,and improve life.The quality and safety are good,and it is worthy of clinical promotion.