安罗替尼联合化疗对二线化疗失败晚期非小细胞肺癌的疗效分析

Efficacy analysis of anlotinib combined with chemotherapy for advanced non-small cell lung cancer after failure of second-line chemotherapy

目的观察安罗替尼联合化疗对二线化疗失败晚期非小细胞肺癌(NSCLC)患者的疗效及安全性。方法回顾性分析2017年1月至2019年10月安徽医科大学附属巢湖医院肿瘤科收治的80例二线化疗失败的晚期NSCLC患者,根据治疗方案不同,分为对照组(n=36)和观察组(n=44),对照组采用培美曲塞+顺铂治疗,观察组采用培美曲塞+顺铂+安罗替尼治疗。比较两组肿瘤客观缓解率(ORR)、疾病控制率(DCR)、中位无进展生存期(PFS)、总生存期(OS),患者治疗前、后血清血管内皮生长因子(VEGF)、癌胚抗原(CEA)、糖类抗原199(CA199)水平变化以及治疗相关不良反应。结果治疗2个周期后,对照组和观察组患者ORR分别为5.56%(2/36)、18.18%(8/44),差异无统计学意义(χ^(2)=1.85,P=0.174);对照组、观察组DCR分别为58.33%(21/36)、81.82%(36/44),观察组DCR明显高于对照组,差异具有统计学意义(χ^(2)=5.33,P=0.021)。对照组和观察组患者中位PFS分别为4.0个月、6.0个月,观察组明显长于对照组,差异有统计学意义(χ^(2)=28.47,P<0.001);两组患者中位OS分别为13.0个月、14.8个月,差异无统计学意义(χ^(2)=1.56,P=0.212)。治疗2个周期后两组患者血清VEGF[(21.72±5.42)ng/Lvs.(36.97±7.53)ng/L,t=14.13,P<0.001;(16.61±4.14)ng/Lvs.(38.85±8.61)ng/L,t=23.09,P<0.001]、CEA[(4.91±1.58)ng/mlvs.(6.62±2.84)ng/ml,t=4.64,P<0.001;(3.07±1.32)ng/mlvs.(7.08±3.31)ng/ml,t=11.50,P<0.001]、CA199[(16.83±5.23)U/mlvs.(20.95±7.94)U/ml;t=3.75,P<0.001;(13.37±5.85)U/mlvs.(21.66±8.72)U/ml,t=7.55,P<0.001]水平均较治疗前明显下降,且治疗后观察组血清VEGF、CEA、CA199水平均明显低于对照组(t=4.78,P<0.001;t=5.68,P<0.001;t=2.76,P=0.007)。观察组血压升高发生率明显高于对照组[25.00%(11/44)vs.2.78%(1/36),χ^(2)=7.67,P=0.006]。结论培美曲塞+顺铂+安罗替尼方案用于二线化疗失败的晚期NSCLC患者治疗,可提高DCR、延长患者PFS,改善血清肿瘤相关标志物水平,不良反应可控。

Objectiv e To observe the efficacy and safety of anlotinib combined with chemotherapy in patients with advanced non-small cell lung cancer(NSCLC)who failed second-line chemotherapy.Methods A retrospective analysis was performed on 80 patients with advanced NSCLC who had failed second-line chemotherapy admitted in the Department of Oncology of Chaohu Hospital of Anhui Medical University from January 2017 to October 2019,and the patients were divided into control group(n=36)and observation group(n=44)according to the different treatment regimens.The control group was given pemetrexed+cisplatin,and the observation group adopted pemetrexed+cisplatin+anlotinib.The objective response rate(ORR),disease control rate(DCR),median progression-free survival(PFS),overall survival(OS),changes in levels of serum vascular endothelial growth factor(VEGF),carcinoembryonic antigen(CEA)and carbohydrate antigen 199(CA199)and treatment-related adverse reactions were compared between the two groups.Results After 2 cycles of treatment,the ORR in the control group and observation group were 5.56%(2/36)and 18.18%(8/44),with no statistically significant difference(χ^(2)=1.85,P=0.174).The DCR in the two groups were 58.33%(21/36)and 81.82%(36/44),and the DCR in the observation group was significantly higher than that in the control group,with a statistically significant difference(χ^(2)=5.33,P=0.021).The median PFS in the two groups were 4.0 months and 6.0 months,and the median PFS in the observation group was longer than that in the control group,with a statistically significant difference(χ^(2)=28.47,P<0.001).The median OS in the two groups were 13.0 months and 14.8 months,with no statistically significant difference(χ^(2)=1.56,P=0.212).The levels of serum VEGF[(21.72±5.42)ng/L vs.(36.97±7.53)ng/L,t=14.13,P<0.001;(16.61±4.14)ng/L vs.(38.85±8.61)ng/L,t=23.09,P<0.001],CEA[(4.91±1.58)ng/ml vs.(6.62±2.84)ng/ml,t=4.64,P<0.001;(3.07±1.32)ng/ml vs.(7.08±3.31)ng/ml,t=11.50,P<0.001]and CA199[(16.83±5.23)U/ml vs.(20.95±7.94)U/ml,t=3.75,P<0.001;(13.37±5.85)U/ml vs.(21.66±8.72)U/ml,t=7.55,P<0.001]in the control group and observation group after 2 cycles of treatment were significantly decreased compared with those before treatment,and the levels of serum VEGF,CEA and CA199 in the observation group were significantly lower than those in the control group(t=4.78,P<0.001;t=5.68,P<0.001;t=2.76,P=0.007).The incidence of elevated blood pressure in the observation group was significantly higher than that in the control group[25.00%(11/44)vs.2.78%(1/36),χ2=7.67,P=0.006].Conclusion Pemetrexed+cisplatin+anlotinib regimen for patients with advanced NSCLC who failed second-line chemotherapy can improve DCR,prolong PFS and improve the levels of serum tumor-related markers,with controllable adverse reactions.