纳武利尤单抗联合DP方案超选择性支气管动脉栓塞灌注治疗晚期非小细胞肺癌的临床研究

Clinical study of nivolumab combined with DP scheme in treatment of advanced non-small cell lung cancer by superselective bronchial arterial embolization

目的探讨纳武利尤单抗联合DP方案超选择性支气管动脉栓塞灌注治疗晚期非小细胞肺癌(NSCLC)患者的临床疗效。方法选取2018年12月-2020年12月在成都医学院第一附属医院呼吸与危重症医学科收治的晚期NSCLC患者187例,将患者按照治疗方法分为对照组(92例)和观察组(95例)。对照组使用超选择支气管动脉栓塞灌注化疗治疗,输注2000 mL 0.9%氯化钠溶液或糖盐水水化,0.9%氯化钠溶液100 mL分别稀释多西他赛注射液及顺铂注射液,37.5 mg/m^(2),先缓慢注入稀释后多西他赛,间隔30 min再注入稀释后顺铂。灌注化疗间隔3周,共4个疗程。观察组患者在对照组的基础上静脉输注纳武利尤单抗注射液,3 mg/kg,每2周用药1次,直至患者不耐受或病情进展。观察两组患者临床疗效,比较治疗前后Karnofsky功能状态评分(KPS)、肿瘤标志物和T淋巴细胞亚群变化以及化疗期间不良反应情况。结果治疗后,观察组的总有效率为65.26%,显著高于对照组的40.22%,两组比较差异具有统计学意义(P<0.05)。治疗后,两组患者KPS评分较化疗前均增加(P<0.05),且观察组KPS评分增加程度明显较对照组大(P<0.05)。治疗后,两组患者血清癌抗原125(CA125)、癌胚抗原(CEA)、CYFRA21-1水平较化疗前降低(P<0.05);且观察组肿瘤标志物水平显著低于对照组(P<0.05)。治疗后,对照组患者CD3+、CD4+和CD4+/CD8+均显著降低(P<0.05),而观察组患者显著升高(P<0.05);观察组免疫功能指标显著优于对照组(P<0.05)。两组患者化疗期间不良反应发生率比较差异无统计学意义。结论纳武利尤单抗联合DP方案超选择性支气管动脉栓塞灌注治疗对晚期NSCLC患者近期疗效良好,且可以改善患者生存资料和免疫功能,降低肿瘤标志物水平,不良反应轻,患者耐受性较好。

Objective To investigate the clinical efficacy of nivolumab combined with DP scheme in treatment of advanced nonsmall cell lung cancer by superselective bronchial arterial embolization.Methods A total of 187 patients with advanced NSCLC who were admitted to the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Chengdu Medical College from December 2018 to December 2020 were selected and divided into control group(92 cases)and observation group(95 cases)according to treatment methods.Patients in the control group was treated with superselective bronchial arterial embolization and perfusion chemotherapy,with 2000 mL normal saline or sugar saline hydration,and 100 mL 0.9%sodium chloride solution to dilute Docetaxel injection and Cisplatin injection,respectively,at 37.5 mg/m^(2).Docetaxel was slowly injected first and then diluted,and then diluted cisplatin was injected at an interval of 30 min.There were 4 courses of infusion chemotherapy at an interval of 3 weeks.Observation group received intravenous infusion of Nivolumab injection,3 mg/kg,once every 2 weeks,on the basis of control group,until patients’intolerance or disease progression.Clinical efficacy was observed between two groups.Changes in Karnofsky functional status score(KPS),tumor markers,T lymphocyte subsets,and adverse reactions during chemotherapy were compared before and after treatment.Results After treatment,the total effective rate of the observation group was 65.26%,significantly higher than that of the control group(40.22%),and the difference between two groups was statistically significant(P<0.05).After treatment,KPS scores in two groups were increased compared with those before chemotherapy(P<0.05),and the increase degree of KPS scores in observation group was significantly greater than that in control group(P<0.05).After treatment,the levels of serum CA125,CEA and CYFRA21-1 in two groups were lower than those before chemotherapy(P<0.05).The level of tumor markers in the observation group was significantly lower than that in the control group(P<0.05).After treatment,CD3+,CD4+and CD4+/CD8+in control group were significantly decreased(P<0.05),while in observation group,they were significantly increased(P<0.05).The immune function indexes of observation group were significantly better than those of control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups during chemotherapy.Conclusion Nivolumab combined with DP scheme in treatment of advanced non-small cell lung cancer by superselective bronchial arterial embolization has good short-term efficacy,and can improve the survival data and immune function of patients,reduce the level of tumor markers,and have mild adverse reactions and good tolerance in patients.