贝伐珠单抗联合培美曲塞治疗老年晚期肺腺癌的临床疗效及对机体免疫功能的影响

Clinical Efficacy of Bevacizumab Combined with Pemetrexed in the Treatment of Advanced Lung Adenocarcinoma in the Elderly and its Effects on Immune Function

目的:探讨贝伐珠单抗联合培美曲塞治疗老年晚期肺腺癌的临床疗效及对机体免疫功能的影响。方法:采用前瞻性队列研究设计,纳入2015年8月至2018年12月首都医科大学大兴教学医院收治的符合入组标准的晚期肺腺癌患者,根据治疗方案的不同分为对照组和研究组。对照组40例患者给予培美曲塞500 mg/m^2,静脉滴注,仅第1日给药,每21 d为1个周期。研究组42例患者给予培美曲塞500 mg/m^2,静脉滴注,仅第1日给药,每21 d为1个周期;贝伐珠单抗7.5 mg/kg,静脉滴注,仅第1日给药,每14 d为1个周期。两组患者均接受至少4个周期的化疗,4个周期后比较两组患者的临床疗效、不良反应及外周血免疫指标变化,并随访疾病无进展生存期(progression free survival,PFS)。结果:研究组、对照组患者的客观有效率分别为52.4%(22/42)、37.5%(15/40),差异无统计学意义(P=0.176);疾病控制率分别为83.3%(35/42)、62.5%(25/40),差异有统计学意义(P=0.033)。研究组患者的中位PFS为6.5个月(95%CI:5.82~7.29个月),对照组患者的PFS为5.2个月(95%CI:4.45~5.97个月),两组比较,差异有统计学意义(P=0.04)。两组患者主要的3/4级不良反应包括中性粒细胞减少、血小板减少、贫血、恶心呕吐、乏力、高血压及蛋白尿,两组患者各不良反应发生率的差异均无统计学意义(P>0.05)。对照组患者治疗后T细胞亚群、自然杀伤细胞(NK细胞)活性、免疫球蛋白A(IgA)和免疫球蛋白M(IgM)水平明显降低,与治疗前比较的差异均有统计学意义(P<0.05);研究组患者治疗后T细胞亚群、NK细胞活性、IgA和IgM水平较治疗前降低不明显,与对照组治疗后的差异均有统计学意义(P<0.05)。治疗前后,两组患者IgG水平组内、组间比较,差异均无统计学意义(P>0.05)。结论:贝伐珠单抗联合培美曲塞治疗老年晚期肺腺癌的疗效确切,疾病控制率优于培美曲赛单药治疗,不良反应可耐受,对外周血免疫指标水平的影响相对较小。

OBJECTIVE:To probe into the clinical efficacy of bevacizumab combined with pemetrexed in the treatment of advanced lung adenocarcinoma in the elderly and its effects on immune function.METHODS:Prospective cohort study design was adopted.Patients with advanced lung adenocarcinoma who met the inclusion criteria and admitted into Daxing Teaching Hospital,Capital Medical University from Aug.2015 to Dec.2018 were divided into the control group and the study group according to different treatment regimens.Forty patients in the control group were given pemetrexed 500 mg/m^2 intravenously,and the drug was administered only on the first day,with 21 d for one cycle.Forty-two patients in the study group received pemetrexed 500 mg/m^2 intravenously,and the drug was administered only on the first day,with 21 d for one cycle;bevacizumab 7.5 mg/kg intravenously,and the drug was administered only on the first day,with 14 d for one cycle.Both groups received at least 4 cycles of chemotherapy,and after 4 cycles,the clinical efficacy,adverse drug reactions,and peripheral blood immune indicators were compared between two groups,and the disease progression-free survival(PFS)was followed up.RESULTS:The objective effective rates in the study group and the control group were 52.4%(22/42)and 37.5%(15/40),respectively,with no statistically significant difference(P=0.176);the disease control rates were respectively 83.3%(35/42)and 62.5%(25/40),with statistically significant differences(P=0.033).The median PFS of the study group was 6.5 months(95%CI:from 5.82 to 7.29 months),while that of the control group was 5.2 months(95%CI:from 4.45 to 5.97 months),the difference was statistically significant(P=0.04).The main grade 3/4 adverse drug reactions in two groups were neutropenia,thrombocytopenia,anemia,nausea and vomiting,fatigue,hypertension and proteinuria,and the difference was not statistically significant(P>0.05).T cell subsets,NK cell activity,IgA and IgM levels in the control group decreased significantly after treatment,and the differences were statistically significant compared with those before treatment(P<0.05).T cell subsets,NK cell activity,IgA and IgM levels in the study group did not decrease significantly after treatment,and the difference was statistically significant compared with those in the control group after treatment(P<0.05).Before and after treatment,there was no statistically significant difference in IgG levels between two groups(P>0.05).CONCLUSIONS:The efficacy of bevacizumab combined with pemetrexed in the treatment of advanced lung adenocarcinoma in the elderly is significant,the disease control rate was superior to pemetrexacin monotherapy,with tolerable adverse drug reactions,and the effects on the level of peripheral immune indicators are small.