安罗替尼联合化疗二线治疗酪氨酸激酶抑制剂获得性耐药晚期非小细胞肺癌临床观察  

Anlotinib combined with chemotherapy in second-line treatment with acqured tyrosine kinase inhibitors resistant and advanced non-small cell lung cancer:A clinical observation

作　　者：王伟英[1] 董良[1] 李海金[1] 李英[1] 尚官敏[1] 葛丽娜[1] 戚丽萍 赵建刚[1] 彭登付 WANG Wei-ying;DONG Liang;LI Hai-jin;LI Ying;SHANG Guan-min;GE Li-na;QI Li-ping;ZHAO Jian-gang;PENG Deng-fu(Department of Oncology Medicine,Shaoxing Hospital,China Medical University,Shaoxing312030,P.R.China)

机构地区：[1]中国医科大学绍兴医院肿瘤内科,浙江绍兴312030

出　　处：《中华肿瘤防治杂志》2020年第20期1669-1673,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)已经成为驱动基因阳性晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一线标准治疗,而TKI耐药的后线治疗则是临床研究的热点和难点。本研究探讨抗血管生成靶向药物安罗替尼联合培美曲塞+卡铂二线治疗TKI获得性耐药后晚期NSCLC的近期疗效和安全性。方法纳入中国医科大学绍兴医院2018-06-10-2019-02-01病理确诊为非鳞癌、TKI治疗后疾病进展、二次基因检测T790m阴性的ⅢB/Ⅳ期NSCLC 34例,依时间顺序用数字表法按2∶1随机分为研究组22例和对照组12例。研究组安罗替尼10(患者体质量<60kg)或12mg(患者体质量>60kg),口服,1次/d,用药2周停1周,同时联合全身化疗:培美曲塞500mg/m^2,持续静脉滴入20min,d1;卡铂AUC=5,持续静脉滴入2h,d1,21d为1个治疗周期,每完成2个治疗周期评价1次疗效,患者出现疾病进展(progressive disease,PD)则为研究终点计算无进展生存期(progression-free survival,PFS),或患者出现不能耐受的不良反应则退出研究继续随访至PD计算PFS。对照组单用培美曲塞+卡铂化疗。观察2组患者治疗总有效率(overall response rate,ORR)、疾病控制率(disease control rate,DCR)、PFS和不良反应。结果研究组和对照组ORR分别为54.55%(12/22)和25.00%(3/12),研究组有优势,而差异无统计学意义,χ^2=2.749,P=0.097。DCR分别为90.91%(20/22)和58.33%(7/12),差异有统计学意义,χ^2=5.040,P=0.025。中位PFS分别为6.7和3.5个月,差异有统计学意义,χ^2=12.085,P=0.001。常见不良反应包括骨髓抑制、胃肠道反应、肝肾功能异常和乏力等,2组比较差异无统计学意义,P>0.05。甲状腺功能异常、咯血、蛋白尿和口腔黏膜炎等不良反应研究组略高于对照组,差异无统计学意义,P>0.05。而高血压、手足综合征等不良反应发生率研究组明显高于对照组,差异有统计学意义,P<0.05。1例Ⅲ级手足综合征、1例Ⅲ级口腔黏OBJECTIVE Tyrosine kinase inhibitors(TKIs)have become the first-line therapy for non-small cell lung cancer(NSCLC)cases with driver mutations,while further treatment after development of TKI resistance have been difficult and it is currently under intensive investigation.This study explored the short-term efficacy and safety of anti-vascular targeting drug Anlotinib combined with Pemetrexed+Carboplatin to treat TKI-resistant NSCLC.METHODS The subjects were 34 patients with StageⅢB/Ⅳ NSCLC who were admitted to Shaoxing Hospital of China Medical University from 2018-06-10 to 2019-02-01,diagnosed with non-squamous cell carcinoma,treated with TKI before but developed resistance,and T790 m-negative in the second genetic test.Using a random number table,the subjects were divided at a ratio of 2∶1 into a test group of 22 and a control group of 12.Treatment regimen for the test group was:Anlotinib at 10 mg(patient weight<60 kg)or 12 mg(patient weight>60 kg),oral,once a day,continuously for 2 weeks followed by a week gap;systemic chemotherapy with Pemetrexed at 500 mg/m^2,intravenous infusion in 20 minutes,d1,and Carboplatin to AUC=5,intravenous infusion in 2 hours,d1.The control group was treated with Pemetrexed+Carboplatin only using the same regimen as the test group.Efficacy was evaluated every 2 cycles until disease progression(PD).If a patient withdrew from treatment due to intolerable side effects,the patient would be followed up until PD.Overall response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and adverse effects(AE)were assessed and compared between the two groups.RESULTS The ORR of the test gruop and the control group were 54.55%vs.25.00%,the test group had advantages,but the difference was not statistically significant(χ^2=2.749,P=0.097),DCR was 90.91%vs.58.33%(χ^2=5.040,P=0.025);and PFS was 6.7 months vs.3.5 months(χ^2=12.085,P=0.001).Incidences of common AEs,including bone marrow suppression,gastrointestinal reactions,liver and kidney dysfunction,and fatigue,showed no signif

关 键 词：安罗替尼 培美曲塞 卡铂 酪氨酸激酶抑制剂 获得性耐药 非小细胞肺癌 近期疗效 不良反应 

分 类 号：R734.2[医药卫生—肿瘤]