回生口服液联合化疗、免疫治疗调节PD-1/PD-L1信号通路对晚期NSCLC的效果及安全性

Efficacy and safety of Huisheng oral liquid combined with chemotherapy and immunotherapy on advanced non-small cell lung cancer by regulating the PD-1/PD-L1 signaling pathway

目的探讨回生口服液联合免疫治疗、化疗通过调节PD-1/PD-L1信号通路治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及安全性。方法选取2019年2月至2020年8月60例晚期NSCLC患者,随机分为2组,每组30例。对照组予以信迪利单抗联合紫杉醇+卡铂化疗方案,观察组于对照组基础上予以回生口服液治疗。21 d为1个周期,直至4周期结束。比较2组治疗前、治疗2个周期、治疗4个周期血清肿瘤标志物[细胞角蛋白19片段抗原21-1(CYDRA21-1)、人鳞状细胞癌相关抗原(SCCAg)、癌胚抗原(CEA)]、T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+))、程序性死亡受体(PD)-1/PD-L1信号通路相关指标及临床疗效、安全性、生活质量改善情况、无进展生存期(PFS)、总生存期(OS)。结果观察组客观缓解率(ORR)、疾病控制率(DCR)分别为73.33%、93.33%,高于对照组的46.67%、73.33%(P<0.05);观察组骨髓抑制、脱发、胃肠道反应发生率分别为16.67%、16.67%、36.67%低于对照组43.33%、50.00%、70.00%(P<0.05);观察组生活质量改善率56.67%,高于对照组的30.00%(P<0.05);治疗2、4个周期后观察组血清CYDRA21-1、SCCAg及CEA水平较对照组下降(P<0.05);治疗2、4个周期后观察组CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)较对照组升高(P<0.05);治疗2、4个周期后观察组外周血CD+4T细胞PD-1、PD-L1水平较对照组下降(P<0.05);观察组中位PFS、中位OS分别为8个月、12个月长于对照组的6个月、9个月(P<0.05)。结论回生口服液联合免疫治疗、化疗能改善晚期NSCLC患者生活质量,调节患者免疫功能,抑制血清肿瘤相关因子表达,减轻部分化疗不良反应,延长患者生存期,疗效确切,这可能与调节PD-1/PD-L1信号通路有关。

Objective To investigate the efficacy and safety of Huisheng oral liquid combined with immunotherapy and chemotherapy in the treatment of advanced non-small cell lung cancer(NSCLC)by regulating the programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)signaling pathway.Methods A total of 60 patients with advanced NSCLC in our hospital from February 2019 to August 2020 were randomly divided into control group(n=30)and observation group(n=30).All patients were given sintilimab combined with chemotherapy(carboplatin plus paclitaxel),and those in the observation group were additionally given Huisheng oral liquid.Patients were treated with 4 cycles,with 21 days per cycle.Serum tumor markers(cytokeratin 19 fragment antigen 21-1[CYDRA21-1],human squamous cell carcinoma associated antigen(SCCAg),carcinoembryonic antigen[CEA]),T lymphocyte subsets(CD3^(+),CD4^(+),CD4^(+)/CD8^(+)),and the PD-1/PD-L1 signaling pathway were compared between the two groups before treatment,and after 2 and 4 treatment cycles.In addition,the efficacy,safety,improvement of quality of life,progression-free survival(PFS),and overall survival(OS)were assessed.Results The objective remission rate(ORR,73.33%vs 46.67%)and disease control rate(DCR,93.33%vs 73.33%)in the observation group were significantly higher than those in the control group(P<0.05).The incidence rates of bone marrow suppression(16.67%vs 43.33%),alopecia(16.67%vs 50.00%)and gastrointestinal reaction(36.67%vs 70.00%)in the observation group were significantly lower than those in the control group(P<0.05).The improvement rate of quality of life in observation group was significantly higher than that in control group(56.67%vs 30.00%,P<0.05).After 2 and 4 cycles of treatment,the serum levels of CYDRA21-1,SCCAg and CEA in the observation group were significantly lower than those in control group(P<0.05).The levels of CD3^(+),CD4^(+)and CD4^(+)/CD8^(+)in the observation group were significantly higher than those in control group(P<0.05).PD-1 and PD-L1 levels in peripheral blood CD4^(+)T cells in the observation group were significantly lower than those in the control group(P<0.05).The median PFS(8 months vs 6 months)and OS(12 months vs 9 months)of the observation group were significantly longer than those of the control group.Conclusion Huisheng oral liquid combined with immunotherapy and chemotherapy can improve the quality of life of patients with advanced NSCLC,regulate the immune function,lower serum tumor markers,alleviate some adverse events of chemotherapy,and prolong the survival.The acceptable curative effect is related to the regulation of the PD-1/PD-L1 signaling pathway.