PD-1抑制剂Pembrolizumab联合培美曲塞治疗非小细胞肺癌的疗效观察

Effect of PD-1 Inhibitor Pembrolizumab Combined with Pemetrexed on CYFRA21-1、CEA and CA125 Levels in Postoperative Patients with Non-Small-Cell Lung Cancer

目的探讨PD-1抑制剂Pembrolizumab联合培美曲塞治疗非小细胞肺癌的疗效及对术后患者CYFRA21-1、CEA及CA125水平的影响。方法选取笔者医院胸外科2015年3月~2016年7月收治的非小细胞肺癌患者114例,随机分为观察组(n=56)和对照组(n=58)。对照组患者给予培美曲塞和卡铂进行治疗,观察组患者在此化学治疗基础上加用Pembrolizumab治疗。观察两组患者的临床疗效,中位反应时间、中位OS和中位PFS,治疗前后血清肿瘤标志物水平变化并进行比较分析。结果观察组部分缓解率为55.36%,远高于对照组29.31%,观察组临床疗效(有效率为87.50%)明显优于对照组(有效率为70.69%),两组比较,差异有统计学意义(P<0.05)。观察组中位反应时间为1.7个月,低于对照组2.5个月,(P=0.042);观察组中位OS为15.4个月,高于对照组7.6个月(P=0.034);观察组中位PFS为10.3个月,高于对照组4.2个月(P=0.012)。治疗前两组患者血清肿瘤标志物水平比较,差异无统计学意义(P>0.05);治疗后两组患者的CYFRA21-1、CEA、CA125水平均低于治疗前,且随着治疗时间的延长,CYFRA21-1、CEA、CA125水平呈下降趋势,治疗12周后,观察组CYFRA21-1、CEA、CA125水平分别为10.59±3.18ng/ml,11.65±4.82ng/ml,58.16±12.47U/ml,明显低于对照组15.26±4.73ng/ml,17.42±6.59ng/ml,65.34±11.52U/ml,差异有统计学意义(P<0.05)。两组患者均出现贫血、中性粒细胞减少、急性肾损伤等不良反应,其中贫血发生率较高,观察组为10.71%,对照组为13.79%,其他不良反应发生率均低于5%。观察组不良反应总发生率为30.36%,与对照组(29.31%)比较,差异无统计学意义(P>0.05)。结论PD-1抑制剂Pembrolizumab联合培美曲塞和卡铂治疗非小细胞肺癌治疗效果(以下简称疗效)显著,能明显降低中位反应时间,提高中位PFS,延长患者的生存时间,并且明显降低血清肿瘤标志物CYFRA21-1、CEA及CA125水平,不良反应发生率低,值得临床推广应用。

Objective To investigate the efficacy of PD-1 inhibitor Pembrolizumab combined with pemetrexed on non-small cell lung cancer and its effect on CYFRA21-1,CEA and CA125 levels in postoperative patients.Methods Totally 114 patients with lung cancer were randomly divided into observation group (56 cases) and control group (58 cases).Patients in the control group were treated with pemetrexed and carboplatin,while patients in the observation group were treated with Pembrolizumab on the basis of chemotherapy.The clinical efficacy,median reaction time,median OS and median PFS,the changes of serum tumor markers before and after treatment were observed and compared.Results The partial remission rate of the observation group was 55.36%,much higher than that of the control group (29.31%).The clinical efficacy of the observation group (87.50%) was significantly better than that of the control group (70.69%).The difference between the two groups was significant (P <0.05).The median reaction time of the observation group was 1.7 months,which was lower than that of the control group for 2.5 months.The median PFS of the observation group was 10.3 months,which was significantly longer than that of the control group for 4.2 months.The difference was statistically significant ( P <0.05).There was no significant difference in serum tumor markers between the two groups before treatment ( P >0.05).After treatment,the levels of CYFRA21-1,CEA and CA125 in the two groups were lower than those before treatment,and the levels of CYFRA21-1,CEA and CA125 decreased with the prolongation of treatment time.After 12 weeks of treatment,the levels of CYFRA21-1,CEA and CA125 in the observation group were 10.59±3.18ng/ml,11.65±4.82ng/ml,58.16±12.47U/ml respectively,which were significantly lower than those in the control group 15.26±4.73ng/ml,17.42±6.59ng/ml,65.34±11.52U/ml respectively.The difference was statistically significant ( P <0.05).Anemia,neutropenia,acute kidney injury and other adverse reactions occurred in both groups.The incidence of anemia was 10.71% in the observation group and 13.79% in the control group.The incidence of other adverse reactions were lower than 5%.The total incidence of adverse reactions in the observation group was 30.36%,which was not significantly different from that in the control group (29.31%)( P >0.05).Conclusion Pembrolizumab combined with pemetrexed and carboplatin is effective in the treatment of non-small cell lung cancer.It can significantly decrease the median reaction time,improve the median PFS,prolong the survival time of patients,and significantly decrease the levels of serum tumor markers CYFRA21-1,CEA and CA125.The incidence of adverse reactions is low.It is worthy of clinical application.