阿帕替尼治疗晚期恶性肿瘤的临床疗效及预后因素分析

Analysis of clinical efficacy and prognostic factors of apatinib in the treatment of advanced malignant tumors

目的观察阿帕替尼治疗晚期恶性肿瘤的临床疗效及安全性,并分析影响患者生存的预后因素.方法对2015年2月至2018年7月在山东大学附属济南市中心医院接受阿帕替尼治疗的100例晚期经治恶性肿瘤患者的临床资料进行回顾性分析,评价其临床疗效,并记录相关不良反应,采用Cox回归模型进行单因素和多因素分析,分析患者无进展生存期(PFS)和总生存期(OS)的预测因素.结果 100例二线及二线以上治疗的晚期恶性肿瘤患者中,完全缓解0例(0),部分缓解22例(22%),病情稳定58例(58%),疾病进展20例(20%),客观缓解率为22%(22/100),疾病控制率为80%(80/100),患者中位PFS为3.6个月(95% CI为2.7 ~4.5个月),中位OS为7.0个月(95% CI为4.7~9.3个月).单因素分析结果显示,美国东部肿瘤协作组(ECOG)评分(HR=0.340,95% CI为0.211 ~0.546,P<0.001)、肿瘤原发部位(HR=1.757,95% CI为1.053 ~2.932,P=0.031)、中性粒细胞与淋巴细胞比值(NLR)(HR=0.389,95% CI为0.227 ~0.666,P=0.001)、血红蛋白(HR=1.696,95% CI为1.023 ~2.813,P=0.041)、蛋白尿(HR=1.790,95% CI为1.105 ~3.155,P=0.044)与患者PFS相关;年龄(HR=2.082,95% CI为1.320 ~3.285,P=0.002)、ECOG评分(HR=0.206,95% CI为0.123 ~0.344,P<0.001)、肿瘤原发部位(HR=1.784,95% CI为1.077 ~2.954,P=0.025)、NLR(HR=0.410,95% CI为0.238 ~0.704,P=0.001)、血红蛋白(HR=1.958,95% CI为1.175 ~3.264,P=0.010)、白蛋白(HR=0.467,95% CI为0.277 ~0.787,P=0.004)与患者OS相关.多因素分析结果显示,ECOG评分(HR=0.254,95% CI为0.123 ~0.523,P<0.001)、NLR(HR=0.378,95% CI为0.161 ~0.888,P=0.026)与患者PFS相关;ECOG评分(HR =0.147,95% CI为0.067 ~0.326,P<0.001)、NLR(HR=0.327,95% CI为0.140 ~0.765,P=0.010)、血红蛋白(HR=1.975,95% CI为1.101 ~3.543,P=0.022)与患者OS相关.在安全性方面,100例晚期经治恶性肿瘤患者中最常见的不良反应为高血压53例(53%)、食欲下降51例(51%)、疲劳乏力51例(51%)、贫血50例(50%),其中最常见的3~4级不良反应为高血压10例(10%)、血小板减少8例(8%)、白细胞减少7例(7%)、手足综合征6例(6%).结论阿帕替尼在晚期恶性肿瘤二线及二线以上的治疗中有良好的临床疗效和可控的不良反应.ECOG评分和NLR是预测阿帕替尼治疗晚期恶性肿瘤患者PFS和OS的独立因素.

Objective To observe the clinical efficacy and safety of apatinib in the treatment of advanced malignant tumors and to analyze the prognostic indicators affecting the survival of patients.Methods A total of 100 patients with advanced malignant tumors who were treated with apatinib at Jinan Central Hospital Affiliated to Shandong University from February 2015 to July 2018 were enrolled and their data were analyzed retrospectively.The clinical efficacy was evaluated and the related adverse reactions were recorded.Single and multiple factor analyses were pefformed by Cox regression model.The predictive factors of progression-free survival (PFS) and overall survival (OS) were analyzed.Results One-hundred patients with advanced malignant tumors who were treated with second-line and above treatment were collected.All patients were assessable for response,no complete response was observed,22 patients (22%) achieved partial remission,58 patients (58%) in stable disease,and 20 patients (20%) appeared progressive disease.The objective response rate was 22%(22/100),the disease control rate was 80%(80/100),the median PFS was 3.6 months (95% CI:2.7-4.5 months),and the median OS was 7.0 months (95% CI:4.7-9.3 months).Univariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score (HR =0.340,95% CI:0.211-0.546,P <0.001),tumor primary site (HR =1.757,95% CI:1.053-2.932,P =0.031),neutrophil to lymphocyte ratio (NLR)(HR =0.389,95% CI:0.227-0.666,P =0.001),hemoglobin (HR =1.696,95% CI:1.023-2.813,P =0.041) and proteinuria (HR =1.790,95% CI:1.105-3.155,P =0.044) were related to PFS;age (HR =2.082,95 % CI:1.320-3.285,P =0.002),ECOG score (HR =0.206,95% CI:0.123-0.344,P<0.001),tumor primary site (HR=1.784,95%CI:1.077-2.954,P=0.025),NLR (HR=0.410,95%CI:0.238-0.704,P =0.001),hemoglobin (HR =1.958,95% CI:1.175-3.264,P =0.010) and albumin (HR =0.467,95% CI:0.277-0.787,P =0.004) were related with OS.Multivariate analysis showed that PFS was related to ECOG score (HR =0.254,95% CI:0.123-0.523,P < 0.001) and NLR (HR =0.378,95%CI:0.161-0.888,P =0.026),and OS was related to ECOG score (HR =0.147,95% CI:0.067-0.326,P <0.001),NLR (HR =0.327,95% CI:0.140-0.765,P =0.010) and hemoglobin (HR =1.975,95% CI:1.101-3.543,P =0.022).In term of safety,the most common adverse events among 100 cases of treated patients with advanced malignant tumors were hypertension (53,53 %),anorexia (51,51%),fatigue (51,51%) and anemia (50,50%),among which the most common ones of grade 3 and 4 were hypertension (10,10%),thrombocytopenia (8,8%),leukopenia (7,7%) and hand-foot syndrome (6,6%).Conclusion Apatinib has certain clinical efficacy and manageable adverse events in the treatment of advanced malignant tumors at and above second-line treatment.ECOG score and NLR are independent predictors of PFS and OS in patients with advanced malignant tumors treated with apatinib.