安罗替尼三线及以上治疗晚期非小细胞肺癌近期疗效和生命质量分析

Short-term clinical efficacy and analysis of quality of life of anlotinib in third-line and above treatment for advanced non-small cell lung cancer

目的评价安罗替尼三线及以上治疗晚期非小细胞肺癌的近期疗效、安全性及对患者生命质量的影响。方法给予患者盐酸安罗替尼12 mg,1次/d,服用2周,休息1周,共3周为1周期,直至出现病情进展、不可耐受的不良事件。按照实体瘤疗效评价标准(RECIST)1.1评价疗效,常见不良事件评价标准(CTCAE)4.02评价不良事件,欧洲癌症治疗研究组织(EORTC)QLQ-C30和肺癌专项量表QLQ-LC13测定生命质量变化。结果入组27例患者,无完全缓解患者,部分缓解2例(7.4%),疾病稳定16例(59.3%),疾病进展9例(33.3%),客观缓解率为7.4%,疾病控制率为66.7%。QLQ-C30量表中躯体功能(76.00±10.55∶64.44±11.59)、情绪功能(81.67±8.71∶76.11±6.71)、总体健康状况(48.87±7.97∶40.56±12.49)评分较治疗前升高,差异有统计学意义(t=-4.516,P<0.001;t=-2.646,P=0.019;t=-3.872,P=0.002)。疲乏(50.37±8.95∶40.74±13.86)、恶心呕吐(26.54±16.18∶14.20±11.97)、食欲丧失[M(QR):33.33(33.33)∶33.33(33.33)]症状评分较治疗前升高(t=-2.476,P=0.027;t=-5.036,P<0.001;Z=-2.923,P=0.003);疼痛(28.88±14.23∶33.33±13.60)、呼吸困难[33.33(33.33)∶33.33(66.67)]评分较治疗前降低(t=3.674,P=0.003;Z=-3.266,P=0.001)。QLQ-LC13量表中咳嗽(24.44±19.12∶45.24±20.34)、气促[11.11(22.22)∶33.33(22.22)]、胸痛[0.00(33.33)∶33.33(33.33)]评分较前降低(t=4.000,P=0.001;Z=-4.125,P<0.001;Z=-1.890,P=0.034);口腔疼痛[0.00(33.33)∶0.00(0.00)]及手足刺痛[33.33(33.33)∶0.00(0.00)]评分较治疗前升高(Z=-2.000,P=0.046;Z=-2.264,P=0.024)。常见不良反应有高血压、疲劳、促甲状腺激素升高、蛋白尿、手足综合征、口腔黏膜炎、咯血等,主要为1~2级,对症处理后好转。结论安罗替尼三线及以上治疗晚期非小细胞肺癌疾病控制率较好,不良反应可耐受,可在一定程度上缓解临床症状,改善生命质量。

Objective To evaluate the short-term efficacy, safety and impact on the quality of life of anlotinib in third-line and above treatment for advanced non-small cell lung cancer (NSCLC) patients. Methods All the patients received alotinib 12 mg/d. One cycle was defined as 2 weeks on-treatment followed by 1 week off-treatment until disease progression or treatment intolerance. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to assess tumor responses. Common Terminology Criteria for Adverse Events (CTCAE) 4.02 was used to assess the adverse events. The European Organization for Research on Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 were used to assess quality of life. Results Among 27 patients in study, no complete response (CR) was found, 2 patients (7.4%) achieved partial response (PR), 16 patients (59.3%) achieved stable disease (SD), 9 patients (33.3%) achieved progressive disease (PD), objective response rate (ORR) was 7.4%, and disease control rate (DCR) was 66.7%. The scores of physical functioning (76.00±10.55 vs. 64.44±11.59), emotional functioning (81.67±8.71 vs. 76.11±6.71) and global health status (48.87±7.97 vs. 40.56±12.49) of the QLQ-C30 scale after treatment were higher than those before treatment, with statistically significant differences (t=-4.516, P<0.001;t=-2.646, P=0.019;t=-3.872, P=0.002). Fatigue (50.37±8.95 vs. 40.74±13.86), nausea and vomiting (26.54±16.18 vs. 14.20±11.97), loss of appetite [M(QR): 33.33(33.33) vs. 33(33.33)] were better than before (t=-2.476, P=0.027;t=-5.036, P<0.001;Z=-2.923, P=0.003);pain (28.88±14.23 vs. 33.33±13.60) and dyspnea [33.33(33.33) vs. 33.33(66.67)] scores were lower than before (t=3.674, P=0.003;Z=-3.266, P=0.001). The scores of cough (24.44±19.12 vs. 45.24±20.34), shortness of breath [11.11(22.22) vs. 33.33(22.22)] and chest pain [0.00(33.33) vs. 33.33(33.33)] in the QLQ-LC13 scale after treatment were lower than those before treatment, with statistically significant differences (t=4.000, P=0.001;Z=-4.125, P<0.001;Z=-1.890, P=0.034);the scores of sore mouth or tongue [0.00(33.33) vs. 0.00(0.00)] and hands and feet tingling [33.33(33.33) vs. 0.00(0.00)] were higher than before (Z=-2.000, P=0.046;Z=-2.264, P=0.024). Common adverse reactions included hypertension, fatigue, elevated thyroid stimulating hormone, proteinuria, hand-foot syndrome, oral mucositis, hemoptysis, etc, mainly grade 1-2, and they were all improved after the treatments. Conclusion Anlotinib as a third-line and further therapy is positive effected and well tolerated. It can alleviate the clinical symptoms and significantly improve the quality of life of NSCLC patients.