不同剂量阿帕替尼联合SIB-IMRT在局部复发性老年食管癌患者中的疗效及疗效预测

Efficacy and prediction of different doses of apatinib combined with SIB-IMRT in elderly patients with locally recurrent esophageal cancer

摘要:

目的：探讨不同剂量阿帕替尼联合全程局部同期推量调强放疗（simultaneous integrated boost intensity-modulated radiation therapy，SIB-IMRT）在局部复发性老年食管癌患者中的临床疗效，以及与血清血管内皮细胞生长因子受体-2（vascular endothelial cell growth factor receptor-2，VEGFR-2）、碱性成纤维细胞生长因子（basic fibroblast growth factor，bFGF）的相关性。方法：选取2017年1月至2019年1月河西学院附属张掖人民医院放疗科收治的局部复发性老年食管癌患者126例，随机数字表法分为替吉奥组、阿帕替尼组（0.25 g）、阿帕替尼组（0.5 g），每组42例。所有患者给予食管癌局部复发病灶SIB-IMRT，放疗第1天给予对应药物治疗。主要研究终点：无进展生存期（progression-free survival，PFS）、总生存期（overall survival，OS）；次要研究终点：客观缓解率（objective response rate，ORR）、疾病控制率（disease control rate，DCR）、血清标志物VEGFR-2和bFGF变化、药物不良反应发生率。结果：阿帕替尼组（0.5 g）1例患者因高血压不能耐受，退出临床试验。与替吉奥组相比，阿帕替尼组（0.25 g）和阿帕替尼组（0.5 g）ORR、DCR明显升高（P＜0.05），血清VEGFR-2、bFGF水平明显下降（P＜0.05），骨髓抑制、胃肠反应、乏力发生率明显下降（P＜0.05），高血压、手足综合征、蛋白尿、口腔黏膜反应发生率明显升高（P＜0.05），PFS、OS明显延长（P＜0.05），差异均具有统计学意义。阿帕替尼组（0.5 g）乏力、高血压、手足综合征、口腔黏膜反应发生率明显高于阿帕替尼组（0.25 g）（P＜0.05），差异具有统计学意义；阿帕替尼组（0.5 g）与阿帕替尼组（0.25 g）在ORR、DCR、VEGFR-2、bFGF-6、OS等指标相比较（P＞0.05），差异不具有统计学意义。结论：与替吉奥组相比较，小剂量阿帕替尼（0.25 g）联合SIB-IMRT在局部复发性老年食管癌患者中可提高生存期，安全性好；血清标志物VEGFR-2、bFGF可能为疗效预测潜在标志物。

Abstract:

Objective：To explore the clinical efficacy of different doses of apatinib combined with simultaneous integrated boost intensity-modulated radiation therapy（SIB-IMRT） in elderly patients with locally recurrent esophageal cancer，and its correlation with serum vascular endothelial cell growth factor receptor-2（VEGFR-2） and basic fibroblast growth factor（bFGF）. Methods：A total of 126 elderly patients with locally recurrent esophageal cancer admitted to the Department of Radiotherapy of Zhangye People’s Hospital Affiliated to Hexi University from January 2017 to January 2019 were randomly divided into the S-1 group，the apatinib group（0.25 g），and the apatinib group（0.5 g），with 42 patients in each group. All patients were given SIB-IMRT on a locally recurrent lesion of esophageal cancer，and the corresponding drug was given on the first day of radiotherapy. Primary study endpoints：progression-free survival（PFS），overall survival（OS）；secondary study endpoints：objective response rate（ORR），disease control rate（DCR），changes in serum markers VEGFR-2 and bFGF，and incidence of adverse drug reactions. Results：One patient in the apatinib group（0.5 g） dropped out of the clinical trial due to intolerance of hypertension. Compared with the S-1 group，the ORR and DCR of the apatinib group（0.25 g） and the apatinib group（0.5 g） were significantly increased（P<0.05），the levels of serum VEGFR-2 and bFGF were significantly decreased（P<0.05），the incidence of myelosuppression，gastrointestinal reactions，and fatigue decreased significantly（P<0.05），the incidence of adverse reactions to hypertension，hand-foot syndrome，proteinuria，and oral mucosal reactions significantly increased（P<0.05），and PFS and OS were significantly prolonged（P<0.05）. The differences were statistically significant. The incidence of fatigue，hypertension，hand-foot syndrome，and oral mucosal reactions in the apatinib group（0.5 g） was significantly higher than that in the apatinib group（0.25 g）（P<0.05），with statistical significance. There was no significant difference in the ORR，DCR，VEGFR-2，bFGF-6，OS，and other indicators between the apatinib group（0.5 g） and the apatinib group（0.25 g）（P >0.05）. Conclusion：Compared with the S-1 group，low-dose apatinib（0.25 g） combined with SIB-IMRT can improve survival and safety of elderly patients with locally recurrent esophageal cancer. Serum markers VEGFR-2 and bFGF may be potential markers for predicting therapeutic efficacy.