阿帕替尼治疗晚期胃癌的临床疗效及不良反应

Efficacy and adverse reactions of apatinib in advanced gastric cancer

目的观察阿帕替尼治疗晚期胃癌的临床疗效和不良反应.方法收集2016年1月30日至2017年11月1日山东省淄博市第一医院、山东省淄博市中心医院收治的化疗失败的晚期胃癌患者240例.所有患者口服甲磺酸阿帕替尼850 mg/次,1次/d,28 d为1个周期至疾病进展,评价患者临床疗效、不良反应、无进展生存期(PFS)和总生存期(OS).采用Cox回归模型分析影响患者PFS和OS的危险因素.结果 240例患者中,完全缓解0例,部分缓解25例(10.4%),病情稳定113例(47.1%),疾病进展102例(42.5%),客观缓解率(ORR)为10.4%(25/240),疾病控制率(DCR)为57.5%(138/240).阿帕替尼作为二线治疗药物时,ORR与DCR分别为62.5%(5/8)、75.0%(6/8);三线治疗药物时为13.9%(20/144)、67.4%(97/144);四线治疗药物时为0、52.4%(33/63);五线治疗药物时为0、8.0%(2/25).阿帕替尼的不良反应多样,涉及全身多个器官系统,皮损(65.8%,158/240)、疲乏(57.9%,139/240)、胃肠道反应(45.4%,109/240)、高血压(38.8%,93/240)的发生率较高.Cox多因素分析结果显示,治疗时机(HR=5.028,95% CI为1.130 ~ 15.771,P=0.005)、身体质量指数(BMI)变化(HR=21.069,95%CI为4.521 ~ 127.116,P<0.001)是影响患者PFS的独立危险因素.BMI变化(HR=6.550,95% CI为1.080 ~38.455,P=0.039)是影响OS的独立危险因素.结论对二线及二线以上化疗失败的晚期胃癌患者而言,口服阿帕替尼仍可获得一定的DCR及生存收益.阿帕替尼不良反应类型多样,涉及器官系统广泛,但总体可控.

Objective To investigate the effects and adverse reactions of apatinib in advanced gastric cancer patients.Methods Two hundred and forty cases of advanced gastric cancer patients who had failed chemotherapy were collected from January 30,2016 to November 1,2017 in the First Hospital of Zibo City of Shandong Province and the Central Hospital of Zibo City of Shandong Province.All patients took oral apatinib mesylate,850 mg/time,1 time/d,and 28 d as 1 cycle of treatment,during which clinical efficacy,adverse reaction and progression free survival (PFS) and overall survival period (OS) were evaluated.Adopting Cox regression model to analyze risk factors of PFS and OS.Results Of all 240 patients,no patient reached complete response (CR) standard,25 patients (10.4%) reached partial response (PR) standard,113 patients (47.1%) reached stable disease (SD) standard,and 102 patients (42.5%) reached progressive disease (PD) standard.Objective response rate (ORR) and disease control rate (DCR) were 10.4%(25/240) and 57.5%(138/240) respectively.When apatinib was taken as a 2nd line treatment,ORR and DCR were 62.5%(5/8) and 75.0%(6/8) respectively;as 3rd line treatment,the result came to 13.9%(20/144) and 67.4%(97/144);as 4th line treatment,it was 0 and 52.4%(33/63);as 5th line treatment,it was 0 and 8.0%(2/25).Among the various adverse effects of apatinib,the most common ones observed were skin lesion (65.8%,158/240),fatigue (57.9%,139/240),gastrointestinal reaction (45.4%,109/240),and hypertension (38.8%,93/240).Cox multivariate analysis showed that the change of treatment time (HR =5.028,95%CI:1.130-15.771,P =0.005) and body mass index (HR =21.069,95%CI:4.521-127.116,P < 0.001) were the independent risk factors of PFS.BMI change (HR =6.550,95% CI:1.080-38.455,P =0.039) was independent risk factor of OS.Conclusion For patients with advanced gastric cancer who failed with 2nd line and above chemotherapy,oral atatinib still obtain certain DCR and survival gain.Apatinib adverse reactions are various,involving a wide range of organ systems,however are generally controllable.