摘要
目的探讨程序性死亡蛋白-1(PD-1)抑制剂联合常规化学治疗对非小细胞肺癌(NSCLC)的治疗效果。方法选择2018年1月至2020年5月濮阳市第五人民医院收治的85例NSCLC患者为研究对象,根据治疗方法将患者分为对照组(n=42)和观察组(n=43)。对照组患者给予常规化学治疗,第1天静脉滴注卡铂0.3~0.4 g·m^(-2)、紫杉醇脂质体135~175 mg·m^(-2)、培美曲塞500 mg·m^(-2),2l d为1个周期,1个周期给药1次,连续治疗6个周期。观察组患者在对照组治疗基础上给予PD-1抑制剂派姆单抗,静脉滴注,第1天2 mg·kg^(-1),21 d为1个周期,1个周期给药1次,连续治疗6个周期。治疗后,评估2组患者的临床疗效,并计算总有效率。分别于治疗前后,采用流式细胞术检测2组患者外周血中CD3^(+)、CD4^(+)、CD8^(+)T细胞及辅助性T(Th)1、Th2细胞水平,采用酶联免疫吸附试验检测2组患者血清中干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、白细胞介素-4(IL-4)水平。观察并记录2组患者治疗期间白细胞减少、中性粒细胞减少、恶心呕吐、腹泻、周围神经毒性、皮疹发生情况,并计算不良反应发生率。结果治疗后,对照组患者部分缓解25例,疾病稳定14例,疾病进展3例,总有效率为59.52%(25/42);观察组患者完全缓解1例,部分缓解34例,疾病稳定7例,疾病进展1例,总有效率为81.40%(35/43)。观察组患者的总有效率显著高于对照组(χ2=4.896,P<0.05)。治疗前,2组患者外周血中的CD3^(+)、CD4^(+)、CD8^(+)T细胞及Th1、Th2细胞水平比较差异无统计学意义(P>0.05);2组患者治疗后的CD3^(+)、CD4^(+)T细胞及Th1、Th2细胞水平显著高于治疗前,CD8^(+)T细胞水平显著低于治疗前(P<0.05);治疗后,观察组患者外周血中的CD3^(+)T细胞及Th1细胞水平显著高于对照组(P<0.05);治疗后,观察组与对照组患者外周血中的CD4^(+)、CD8^(+)T细胞及Th2细胞水平比较差异无统计学意义(P>0.05)。治疗前,2组患者血清中IFN-γ、TNF-α、IL-10、IL-4水平比较差异无统计学意义(P>0.05);2组患者治疗后血清中TNF-α、IL-4水平显著低于治疗前,血清中IFN-γ、IL-10水平显著高于治疗前(P<0.05);治疗后,观察组患者血清中IFN-γ水平显著高于对照组(P<0.05);治疗后,2组患者血清中TNF-α、IL-10、IL-4水平比较差异无统计学意义(P>0.05)。治疗过程中,观察组与对照组患者白细胞减少、中性粒细胞减少、恶心呕吐、腹泻、周围神经毒性及皮疹的发生率比较差异无统计学意义(χ2=1.898、1.694、2.173、1.001、0.988、1.838,P>0.05)。结论PD-1抑制剂联合常规化学治疗方案可能通过上调CD3^(+)T细胞、Th1细胞及血清IFN-γ水平发挥对NSCLC患者的抗肿瘤作用,临床疗效显著,可改善患者的免疫功能,降低炎症反应,且安全性好。
Objective To investigate the effect of programmed death protein-1(PD-1)inhibitor combined with conventional chemotherapy in the treatment of non-small cell lung cancer(NSCLC).Methods A total of 85 NSCLC patients admitted to the Fifth People′s Hospital of Puyang City from January 2018 to May 2020 were selected as the research objects,and they were divided into the control group(n=42)and the observation group(n=43)according to the treatment method.The patients in the control group were given conventional chemotherapy,including intravenous infusion of carboplatin 0.3-0.4 g·m^(-2),paclitaxel liposome 135-175 mg·m^(-2),pemetrexed 500 mg·m^(-2) on the first day,2l days as a cycle,once per a cycle,the treatment was continued for 6 cycles.The patients in the observation group were given the PD-1 inhibitor pembrolizumab on the basis of the treatment in the control group,intravenous drip,2 mg·kg^(-1) on the first day,21 days as a cycle,once per a cycle,and the treatment was continued for 6 cycles.After treatment,the clinical efficacy of patients in the two groups was evaluated,and the total effective rate was calculated.Before and after treatment,the levels of CD3^(+),CD4^(+),CD8^(+)T cells and helper T(Th)1 and Th2 cells in peripheral blood of patients in the two groups were detected by the flow cytometry;the levels of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10)and interleukin-4(IL-4)in serum of patients in the two groups were detected by enzyme-linked immunosorbent assay.The incidence of leukopenia,neutropenia,nausea and vomiting,diarrhea,peripheral neurotoxicity and rash of patients in the two groups were observed and recorded during treatment,and the incidences of adverse reactions were calculated.Results After treatment,25 cases had partial remission,14 cases had stable disease,and 3 cases had progressive disease,with a total effective rate of 59.52%(25/42)in the control group;in the observation group,1 case had complete remission,34 cases had partial remission,7 cases had stable disease,and 1 case had disease progression,the total effective rate was 81.40%(35/43).The total effective rate of patients in the observation group was significantly higher than that in the control group(χ2=4.896,P<0.05).Before treatment,there was no significant difference in the levels of CD3^(+)T cells,CD4^(+)T cells,CD8^(+)T cells,Th1 cells and Th2 cells in peripheral blood of patients between the two groups(P>0.05).The levels of CD3^(+)T cells,CD4^(+)T cells and Th1 cells,Th2 cells in peripheral blood of patients in the two groups after treatment were significantly higher than those before treatment,and the level of CD8^(+)T cells was significantly lower than that before treatment(P<0.05);after treatment,the levels of CD3^(+)T cells and Th1 cells in peripheral blood of patients in the observation group were significantly higher than those in the control group(P<0.05);there was no significant difference in the levels of CD4^(+)T cells,CD8^(+)T cells and Th2 cells in peripheral blood of patients between the two groups after treatment(P>0.05).Before treatment,there was no significant difference in serum IFN-γ,TNF-α,IL-10 and IL-4 levels of patients between the two groups(P>0.05).The levels of serum TNF-αand IL-4 of patients after treatment were significantly lower than those before treatment,and the levels of serum IFN-γand IL-10 of patients were significantly higher than those before treatment in the two groups(P<0.05).After treatment,the level of serum IFN-γof patients in the observation group was significantly higher than that in the control group(P<0.05);there was no significant difference in serum TNF-α,IL-10 and IL-4 levels of patients between the two groups(P>0.05).During the treatment,there was no significant difference in the incidences of leukopenia,neutropenia,nausea and vomiting,diarrhea,peripheral neurotoxicity and rash of patients between the two group(χ2=1.898,1.694,2.173,1.001,0.988,1.838;P>0.05).Conclusion PD-1 inhibitor combined with conventional chemotherapy may play an anti-tumor effect on NSCLC patients by up-regulating the levels of CD3^(+)T cells,Th1 cells and serum IFN-γlevel,the clinical efficacy is significant,and it can improve patients′immune function,reduce inflammatory response,and it is good safe.
作者
刘自威
朱华强
王洋
LIU Ziwei;ZHU Huaqiang;WANG Yang(Department of Oncology,the Fifth People′s Hospital of Puyang City,Puyang 457000,Henan Province,China)
出处
《新乡医学院学报》
CAS
2022年第10期948-953,共6页
Journal of Xinxiang Medical University
