阿帕替尼治疗胃癌和食管胃结合部腺癌伴肝转移患者的临床观察

Efficacy of apatinib in the treatment of advanced gastric cancer or esophagogastric junction adenocarcinoma with liver metastases

目的探讨阿帕替尼治疗胃癌和食管胃结合部腺癌伴肝转移患者的临床疗效及安全性。方法收集2011年3月至2017年2月病理组织学确诊为胃癌或食管胃结合部腺癌伴肝转移患者42例,其中18例初治患者,24例复发难治患者。阿帕替尼口服剂量为250~850 mg,同时根据患者体能状态及不良反应给予相应剂量调整;联合化疗方案包括单药替吉奥、XELOX、SOX方案和经导管肝动脉及胃动脉化疗栓塞(TACE),采用RECIST 1.1版标准评价近期疗效,NCI-CTCAE 4.0版标准评价不良反应,分析临床疗效与临床病理特征的关系,随访预后并采用Cox回归模型进行多因素生存分析。结果阿帕替尼联合化疗组的中位化疗周期数为4个(2~6个),中位TACE次数为3次(1~3次);其中PR 3例、SD 22例和PD 17例,有效率(RR)为7.14%,疾病控制率(DCR)为59.52%;中位生存期(OS)为7.0个月,中位无进展生存期(PFS)为2.0个月。患者性别、年龄、原发灶部位、是否行胃切除术、TACE、联合化疗和阿帕替尼不同初始剂量均与RR和DCR无关(P>0.05)。单因素及多因素分析未发现与PFS相关的独立预后因素,是否联合化疗是影响OS的独立预后因素,其中阿帕替尼单药组较联合化疗组的OS差(HR=9.376,95%CI:2.178~40.361,P<0.05)。不良反应包括白细胞减少、贫血、血小板减少、手足综合征、高血压、乏力及腹泻,多为1~2级,发生率低,可耐受。结论阿帕替尼联合化疗治疗胃癌和食管胃结合部腺癌伴肝转移患者临床疗效确切,可明显延长该部分患者生存时间。

Objective To investigate the clinical efficacy and safety of apatinib in the treatment of gastric cancer and esophagogastric junction adenocarcinoma with liver metastases. Methods From Mar. 2011 to Feb. 2017,42 cases of gastric cancer and esophagogastric junction adenocarcinoma with liver metastases including 18 newly diagnosed patients and 24 relapsed refractory patients were analyzed retrospectively. The oral dose range of apatinib was 250-850 mg and the appropriate dose adjustment could be made according to the patients' physical status and side effects. Combined chemotherapy regimens included single drug S-1,XELOX regimen,SOX regimen,and hepatic artery and gastric artery chemoembolization( TACE). The efficacy and adverse effects were respectively evaluated by RECIST 1. 1 and NCI-CTCAE 4. 0 criteria. The relationship between the clinicopathologic features with clinical efficacy was analyzed. The followed-up was performed and Cox regression model was used for multifactor survival analysis. Results In the combined chemotherapy group,the median chemotherapy cycle was 4( 2-6),and the median chemotherapy cycle in the TACE group was 3( 1-3). There were 3 patients( 7. 14%) of PR,22( 52. 38%) cases of SD and 17( 40. 48%) cases of PD. The total response rate( RR) was 7. 14%,and the disease control rate( DCR) was 59. 52%. With a median follow-up time of 4( 1-16) months,the median overall survival( OS) was 7 months and the median progression-free survival( PFS) was 2 months. The clinicapathologic features such as gender,age,primary lesion,gastrectomy,TACE and chemotherapy with different initial does of apatinib was not related to RR or DCR( P>0. 05). Independent prognostic factors of PFS was not found in survival analysis. Apatinib combined with chemotherapy was independent factor of OS. Apatinib monotherapy was associated with a higher risk of death than combined chemotherapy. The side effects included leukocyte decline,anemia,thrombocytopenia,hand foot syndrome,hypertension,fatigue and diarrhea. Most of adverse reactions were in 1-2 grade,whose incidence was low and tolerable. Conclusion Apatinib combined with chemotherapy in the treatment of gastric cancer and esophagogastric junction adenocarcinoma with liver metastases was clinical efficacy, and can significantly extend the survival time.