阿帕替尼治疗晚期胰腺癌的疗效和安全性及疗效预测指标的探索

The efficacy and safety of Apatinib in treatment of advanced pancreatic cancer and exploration of efficacy predictors

目的:观察甲磺酸阿帕替尼治疗晚期胰腺癌的疗效与安全性,探索血清血管内皮生长因子(vascular endothelial growth factor,VEGF)和血管内皮生长因子受体-2(vascular endothelial growth factor receptor-2,VEGFR-2)水平与阿帕替尼疗效的关系。方法:本课题选择经病理确诊一线治疗进展后无法耐受或不愿接受二线化疗的晚期胰腺癌患者,经知情同意后给予阿帕替尼500 mg po qd治疗,2周期评估一次,主要观察指标为疾病控制率(disease control rate,DCR),次要观察指标为无进展生存期(progression-free survival,PFS)和不良反应;应用ELISA法检测治疗前患者血清VEGF和VEGFR-2水平;卡方检验分析血清VEGF和VEGFR-2水平与阿帕替尼疗效的关系。结果:本课题共入组24例一线治疗进展的晚期胰腺癌患者,可评估患者共23例。其中完全缓解(complete response,CR)0例、部分缓解(partial response,PR)1例(4.35%)、疾病稳定(stable disease,SD)8例(34.78%)、疾病进展(progressive disease,PD)14例(60.87%)。DCR为39.13%,中位PFS为2个月。阿帕替尼在治疗过程中出现的不良反应按照发生频率依次为乏力(91.30%)、高血压(52.17%)、口腔黏膜炎(52.17%)、蛋白尿(47.83%)、贫血(43.48%)、腹泻(21.74%)、呕吐(17.39%)、消化道出血(4.35%)、陈旧伤口裂开(4.35%)。在SD组和PD组中血清VEGF和VEGFR-2水平并没有明显差异。结论:对于一线治疗进展并且体力状况良好的晚期胰腺癌患者,阿帕替尼可以作为一个可选的治疗策略,血清VEGF和VEGFR-2水平不能预测阿帕替尼疗效。

Objective:To evaluate the efficacy and safety of Apatinib in advanced pancreatic cancer patients and to investigate the relationship between the expression of vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor-2(VEGFR-2)and efficacy.Methods:In this study,patients with advanced pancreatic cancer who were pathologically diagnosed and who were unable to tolerate or were unwilling to receive second-line chemotherapy after the progression of first-line therapy were selected.After informed consent,they were given Apatinib 500 mg po qd.The patients were evaluated once every 2 cycles.The primary outcome index was disease control rate(DCR),and the secondary outcome indexes were progression-free survival(PFS)and adverse reactions.Serum VEGF and VEGFR-2 levels were detected by ELISA before treatment.Chi-square test was used to analyze the relationship between serum VEGF and VEGFR-2 levels and the efficacy of Apatinib.Results:A total of 24 patients with advanced pancreatic cancer who progressed on first-line therapy were enrolled in this study,and a total of 23 patients were evaluable.Among them,there was 0 case of complete response(CR),1 case(4.35%)of partial response(PR),8 cases(34.78%)of stable disease(SD),and 14 cases(60.87%)of progressive disease(PD).The DCR was 39.13%,and the median PFS was 2 months.The adverse reactions of Apatinib during treatment were fatigue(91.30%),hypertension(52.17%),oral mucositis(52.17%),proteinuria(47.83%),anemia(43.48%),diarrhea(21.74%),vomiting(17.39%),gastrointestinal bleeding(4.35%),old wound dehiscence(4.35%)in order of frequency.There was no significant difference in serum VEGF and VEGFR-2 levels between SD and PD groups.Conclusion:For patients with advanced pancreatic cancer who have progressed on first-line therapy and are in good physical condition,Apatinib can be used as an optional treatment strategy,and serum VEGF and VEGFR-2 levels do not predict Apatinib efficacy.