阿帕替尼联合化疗在晚期非小细胞肺癌患者中的临床疗效和最佳剂量探讨

Clinical efficacy and optimal dose of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer

目的探讨不同剂量阿帕替尼联合化疗在晚期非小细胞肺癌(NSCLC)患者中的临床疗效以及不良反应。方法选取2018年1月至2020年6月中国人民解放军联勤保障部队第九〇一医院确诊的NSCLC患者69例, 按照随机数字表法将患者分为单纯化疗组(采用多西他赛+顺铂化疗)、阿帕替尼A组[采用阿帕替尼(0.25 g)+多西他赛+顺铂治疗]和阿帕替尼B组[采用阿帕替尼(0.50 g)+多西他赛+顺铂治疗], 每组23例。比较3组患者客观缓解率(ORR)、疾病控制率(DCR)、中位总生存期(OS)、中位无进展生存期(PFS)以及不良反应发生率。结果阿帕替尼B组1例患者因发生急性心肌梗塞退出临床研究。治疗4个周期后, 单纯化疗组、阿帕替尼A组和阿帕替尼B组ORR分别为17.39%(4/23)、47.83%(11/23)和54.55%(12/22), 差异具有统计学意义(χ^(2)=7.41, P=0.024);阿帕替尼B组ORR高于单纯化疗组, 差异具有统计学意义(χ^(2)=6.77, P=0.009);阿帕替尼A组和单纯化疗组、阿帕替尼A组和阿帕替尼B组ORR差异均无统计学意义(χ^(2)=4.85, P=0.028;χ^(2)=0.20, P=0.652)。3组患者DCR分别为47.83%(11/23)、78.26%(18/23)和86.36%(19/22), 差异具有统计学意义(χ^(2)=9.03, P=0.011);阿帕替尼B组DCR高于单纯化疗组, 差异具有统计学意义(χ^(2)=7.52, P=0.006);阿帕替尼A组和单纯化疗组、阿帕替尼A组和阿帕替尼B组DCR差异均无统计学意义(χ^(2)=4.57, P=0.033;χ^(2)=0.51, P=0.477)。3组患者中位OS分别为6.8、9.2、9.9个月, 差异有统计学意义(χ^(2)=8.91, P=0.022);与单纯化疗组相比, 阿帕替尼A组和阿帕替尼B组显著延长, 差异均具有统计学意义(χ^(2)=7.25, P=0.036;χ^(2)=8.60, P=0.029);与阿帕替尼A组相比, 阿帕替尼B组虽延长, 但差异无统计学意义(χ^(2)=1.54, P=0.201)。3组患者中位PFS分别为5.2、7.7、8.2个月, 差异有统计学意义(χ^(2)=8.79, P=0.026);与单纯化疗组相比较, 阿帕替尼A组和阿帕替尼B组患者显著延长, 差异均具有统计学意义(χ^(2)=7.01, P=0.039;χ^(2)=8.36, P=0.031);与阿帕替尼A组相比, 阿帕替尼B组虽延长, 但差异无统计学意义(χ^(2)=1.68, P=0.186)。3组患者乏力[34.78%(8/23)vs. 65.22%(15/23)vs. 72.73%(16/22), χ^(2)=7.50, P=0.024]、高血压[4.35%(1/23)vs. 34.78%(8/23)vs. 68.18%(15/22), χ^(2)=20.07, P<0.001]、手足综合征[4.35%(1/23)vs. 43.48%(10/23)vs. 72.73%(16/22), χ^(2)=22.28, P<0.001]、口腔黏膜炎[8.70%(2/23)vs. 39.13%(9/23)vs. 72.73%(16/22), χ^(2)=19.26, P<0.001]发生率差异均有统计学意义;与单纯化疗组相比, 阿帕替尼A组高血压、手足综合征, 阿帕替尼B组乏力、高血压、手足综合征、口腔黏膜炎发生率均升高, 差异均具有统计学意义(χ^(2)=6.77, P=0.009;χ^(2)=9.68, P=0.002;χ^(2)=6.51, P=0.011;χ^(2)=20.00, P<0.001;χ^(2)=22.37, P<0.001;χ^(2)=19.21, P<0.001)。结论阿帕替尼(0.50 g)联合化疗在晚期NSCLC疗效优于单纯化疗, 阿帕替尼(0.25 g)和阿帕替尼(0.50 g)均可延长患者生存期, 但增加治疗剂量不能取得更长生存获益。

Objective To explore the clinical efficacy of different doses of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer(NSCLC)and the adverse reactions.Methods A total of 69 patients with NSCLC diagnosed in the No.901 Hospital of the Chinese People's Liberation Army Joint Logistics Support Force were selected from January 2018 to June 2020,and were divided into chemotherapy alone group(docetaxel+cisplatin was used),apatinib group A[apatinib(0.25 g)+docetaxel+cisplatin was used]and apatinib group B[apatinib(0.50 g)+docetaxel+cisplatin was used]according to random number table method,with 23 cases in each group.The objective response rate(ORR),disease control rate(DCR),median overall survival(OS),median progression-free survival(PFS),and incidences of adverse reactions were compared between the three groups of patients.Results One patients in the apatinib group B withdrew from the study due to acute myocardial infarction.After 4 cycless of treatment,the ORR of the patients in the chemotherapy alone group,apatinib group A and apatinib group B were 17.39%(4/23),47.83%(11/23)and 54.55%(12/22)respectively,with a statistically significant difference(χ^(2)=7.41,P=0.024).The ORR of the apatinib group B was higher than that of the chemotherapy alone group,with a statistically significant difference(χ^(2)=6.77,P=0.009).There were no statistically significant differences in ORR between the apatinib group A and chemotherapy alone group,the apatinib group A and apatinib group B(χ^(2)=4.85,P=0.028;χ^(2)=0.20,P=0.652).The DCR of the patients in the three groups were 47.83%(11/23),78.26%(18/23)and 86.36%(19/22)respectively,with a statistically significant difference(χ^(2)=9.03,P=0.011).The DCR of the apatinib group B was higher than that of the chemotherapy alone group,with a statistically significant difference(χ^(2)=7.52,P=0.006).There were no statistically significant differences in DCR between the apatinib group A and the chemotherapy alone group,the apatinib group A and apatinib group B(χ^(2)=4.57,P=0.033;χ^(2)=0.51,P=0.477).The median OS of the patients in the three groups were 6.8,9.2 and 9.9 months respectively,with a statistically significant different(χ^(2)=8.91,P=0.022).Compared with the chemotherapy alone group,the median OS of the apatinib group A and apatinib group B were significantly prolonged,with statistically significant differences(χ^(2)=7.25,P=0.036;χ^(2)=8.60,P=0.029).Compared with the apatinib group A,the median OS of the apatinib group B was prolonged,but there was no statistically significant different(χ^(2)=1.54,P=0.201).The median PFS of the patients in the three groups were 5.2,7.7 and 8.2 months respectively,with a statistically significant different(χ^(2)=8.79,P=0.026).Compared with the chemotherapy alone group,the median PFS of the apatinib group A and apatinib group B were significantly prolonged,with statistically significant differences(χ^(2)=7.01,P=0.039;χ^(2)=8.36,P=0.031).Compared with the apatinib A group,the median PFS of the apatinib group B was prolonged,but there was no statistically significant different(χ^(2)=1.68,P=0.186).There were statistically significant differences in the incidences of fatigue[34.78%(8/23)vs.65.22%(15/23)vs.72.73%(16/22),χ^(2)=7.50,P=0.024],hypertension[4.35%(1/23)vs.34.78%(8/23)vs.68.18%(15/22),χ^(2)=20.07,P<0.001],hand-foot syndrome[4.35%(1/23)vs.43.48%(10/23)vs.72.73%(16/22),χ^(2)=22.28,P<0.001]and oral mucositis[8.70%(2/23)vs.39.13%(9/23)vs.72.73%(16/22),χ^(2)=19.26,P<0.001]among the three groups.Compared with the chemotherapy alone group,the incidences of hypertension and hand-foot syndrome in the apatinib group A and the incidences of fatigue,hypertension,hand-foot syndrome and oral mucositis in the apatinib group B were increased,with statistically significant differences(χ^(2)=6.77,P=0.009;χ^(2)=9.68,P=0.002;χ^(2)=6.51,P=0.011;χ^(2)=20.00,P<0.001;χ^(2)=22.37,P<0.001;χ^(2)=19.21,P<0.001).Conclusion Apatinib(0.50 g)combined with chemotherapy has better short-term efficacy than chemotherapy alone in advanced NSCLC.Apatinib(0.25 g)and apatinib(0.50 g)can prolong the survival of patients,but increasing the treatment dose can not achieve longer survival benefit.