低剂量阿帕替尼治疗晚期胃癌疗效及安全性分析
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摘要
目的回顾性分析低剂量阿帕替尼治疗晚期胃癌的临床疗效及不良反应。方法收集51例应用阿帕替尼治疗三线及三线以上晚期胃癌患者,早餐后口服500 mg/d,观察不良反应,定期复查评价疗效,随访记录生存时间。结果 CR患者0例,PR患者4例(6.67%),SD患者18例(35.29%),PD患者29例(56.87%),ORR为7.84%(4/51),DCR为43.13%(22/51)。单因素分析ECOG PS评分0～1分患者有效率高于2分患者(P=0.001),合并手足综合征、高血压和蛋白尿,其治疗有效率高于无相应不良反应者(均P<0.05),多因素Logistic回归分析显示:ECOG PS、合并手足综合征、高血压是疗效独立预测因素(均P<0.05)。患者m PFS 3.43个月(95%CI,3.19～3.68),m OS4.36个月(95%CI 3.84～4.90),亚组分析显示:DCR组mOS显著长于PD组(6.32个月vs 2.90个月,P<0.05)。结论低剂量阿帕替尼(500 mg/d)治疗三线及三线以上晚期胃癌疗效确切,安全性良好,不良反应可控。
Objective To retrospectively analyze the clinical efficacy and adverse reactions of low-dose apatinib in the treatment of advanced gastric cancer. Methods 51 patients with third-line or more advanced gastric cancer were treated with apatinib, oral 500 mg/d after breakfast. Adverse reactions were observed, and the efficacy was evaluated regularly. The survival time was followed up. Results There was 0 patient with CR, 4 patients with pulmonary disease(6.67%), 18 patients with SD(35.29%) and 29 patients with PD(56.87%). The percentage of ORR and DCR was 7.84%(4/51) and 43.13%(22/51). Univariate analysis showed that the efficacy was higher in ECOG PS score 0-1 points patients than that in patients with more than 2 points(P=0.001). And the efficacy was higher in patients combined with hand-foot syndrome, hypertension and proteinuria in patients with no corresponding adverse reactions(all P<0.05). Multivariate Logistic regression analysis showed that ECOG PS, combined with hand-foot syndrome and hypertension were independent predictors of efficacy(all P<0.05). The m PFS and the m OS of patients was 3.43 months(95% CI, 3.19 to3.68) and 4.36 months(95% CI 3.84 to 4.90). Subgroup analysis showed that m OS was significantly longer in the DCR group than that in the PD group(6.32 months vs 2.90 months, P<0.05). Conclusion Low-dose apafitinib(500 mg/d) is effective in the treatment of third-line or more advanced gastric cancer, with good safety and controllable adverse reactions.
Objective To retrospectively analyze the clinical efficacy and adverse reactions of low-dose apatinib in the treatment of advanced gastric cancer. Methods 51 patients with third-line or more advanced gastric cancer were treated with apatinib, oral 500 mg/d after breakfast. Adverse reactions were observed, and the efficacy was evaluated regularly. The survival time was followed up. Results There was 0 patient with CR, 4 patients with pulmonary disease(6.67%), 18 patients with SD(35.29%) and 29 patients with PD(56.87%). The percentage of ORR and DCR was 7.84%(4/51) and 43.13%(22/51). Univariate analysis showed that the efficacy was higher in ECOG PS score 0-1 points patients than that in patients with more than 2 points(P=0.001). And the efficacy was higher in patients combined with hand-foot syndrome, hypertension and proteinuria in patients with no corresponding adverse reactions(all P<0.05). Multivariate Logistic regression analysis showed that ECOG PS, combined with hand-foot syndrome and hypertension were independent predictors of efficacy(all P<0.05). The m PFS and the m OS of patients was 3.43 months(95% CI, 3.19 to3.68) and 4.36 months(95% CI 3.84 to 4.90). Subgroup analysis showed that m OS was significantly longer in the DCR group than that in the PD group(6.32 months vs 2.90 months, P<0.05). Conclusion Low-dose apafitinib(500 mg/d) is effective in the treatment of third-line or more advanced gastric cancer, with good safety and controllable adverse reactions.
引文
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[18]Giandomenico Roviello,Andrea Ravelli,Karol Polom,et al.Apatinib:A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer[J].Cancer Letters,2016,372(2):187-191.
[19]Li J,Qin S,Xu J,et al.Apatinib for chemotherapy-refractory advanced Metastatic gastric cancer:Results from a randomized,placebocontrolled,parallel-arm,phase IItrial[J].J Clin Oncol,2013,31(26):3219-3225.
[20]Li J,Qin S,Xu J,et al.Randomized,double-blind,placebocontrolled Phase III Trial of apatinib in patients with chemotherapyrefractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction[J].J Clin Oncol,2016,34(13):1448-1454.
[2]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[3]World Health Organization.Health statistics and information systems:WHO mortality database[EB/OL].2014[2015-08-10].http://who.int/health info/mortali ty_Data/en.
[4]陈万青,李贺,孙可欣,等.2014年中国恶性肿瘤发病和死亡分析[J].中华肿瘤杂志,2018,40(1):5-12.
[5]徐瑞华,姜文奇,管忠震.临床肿瘤内科学[M].北京:人民卫生出版社,2014:411-412.
[6]Zhang HJ.Apatinib for molecular targeted therapy in tumor[J].Drug Des Devel Ther,2015,9(11):6075-6081.
[7]秦叔逵,李进.阿帕替尼治疗胃癌的临床应用专家共识[J].临床肿瘤学杂志,2015,20(9):841-847.
[8]中华人民共和国卫生部医政司.胃癌诊疗规范(2011年版)[J].中国医学前沿杂志(电子版),2012,4(5):62-71.
[9]皋文君,刘砚燕,袁长蓉.国际肿瘤化疗药物不良反应评价系统-通用不良反应术语标准4.0版[J].肿瘤,2012,32(2):142-144.
[10]杨学宁,吴一龙.实体瘤治疗疗效评价标准-RECIST[J].循证医学,2004,4(2):85-90.
[11]中国临床肿瘤学会(CSCO).胃癌诊疗指南(2018.V1)[M].北京:人民卫生出版社,2018:51-52.
[12]陈心足,胡建昆.胃癌规范化诊疗进展[J].华西医学,2018,33(4):379-384.
[13]Qi X,LiuY,Wang W,et al.Management of advanced gastric cancer:An overview of major fingings from meta-anglysis[J].Oncotarget,2016,7(47):78180-78205.
[14]YJ Bang,CE Van,A Feyereislova,et al.Trastuzumab in combination with che-motherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric orgastro-oesophageal junction cancer(ToGA):A phase 3,open-label,ran-domised controlled trial[J].Lancet,2010,376(9742):687-697.
[15]R.A.de Mello,A.M.Marques,A.Araujo.HER2 therapies and gastric cancer:A step forward[J].World J.Gastroenterol,2013,19(37):6165-6169.
[16]CS Fuchs,J Tomasek,CJ Yong,et al.Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(REGARD):Aninternational,randomised,multicentre,placebo-controlled,phase 3 trial[J].Lancet,2014,383(9911):31-39.
[17]Wilke H,Muro K,Van EC,et al.Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(RAINBOW):A double-blind,randomised phase 3 triall[J].Lancet Oncol,2014,15(11):1224-1235.
[18]Giandomenico Roviello,Andrea Ravelli,Karol Polom,et al.Apatinib:A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer[J].Cancer Letters,2016,372(2):187-191.
[19]Li J,Qin S,Xu J,et al.Apatinib for chemotherapy-refractory advanced Metastatic gastric cancer:Results from a randomized,placebocontrolled,parallel-arm,phase IItrial[J].J Clin Oncol,2013,31(26):3219-3225.
[20]Li J,Qin S,Xu J,et al.Randomized,double-blind,placebocontrolled Phase III Trial of apatinib in patients with chemotherapyrefractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction[J].J Clin Oncol,2016,34(13):1448-1454.