阿帕替尼后线治疗标准方案失败的晚期结直肠癌的疗效和安全性及疗效预测因子的初步分析

目的:探讨阿帕替尼后线治疗标准治疗方案失败的晚期结直肠癌患者中的疗效和安全性以及疗效预测因子的初步分析。方法:本研究所需要的样本量用PASS15.0软件进行计算，从2017年5月到2018年10月入组标准方案治疗失败的晚期结直肠癌患者给予阿帕替尼750 mg或500 mg单药治疗。治疗2个周期后评估客观缓解率（ORR），疾病控制率（DCR）。之后随访评价无进展生存期（PFS）和总生存期（OS），并记录治疗过程中出现的不良事件。并对是否出现高血压患者的预后进行关联性分析。本研究的主要研究终点为PFS，次要研究终点为ORR、DCR、OS、安全性数据以及疗效预测因子的初步分析。结果:纳入研究的51例患者中45例患者可以评价疗效及安全性数据。45例接受阿帕替尼治疗的晚期结直肠癌患者的ORR为11.11%，DCR为77.78%。中位无进展生存期（mPFS）为3.95个月。中位总生存期（mOS）为10.3个月。不良事件方面，接受治疗的患者中常见的不良反应有高血压、手足综合征、蛋白尿和腹泻等。其中发生率较高的3级以上不良反应为手足综合征6例（13.33%），高血压5例（11.11%），蛋白尿5例（11.11%），转氨酶升高4例（8.89%）。出现高血压患者的PFS相对于未出现高血压患者的显著较长，并具有统计学差异（P=0.01）。结论:阿帕替尼单药三线及后线治疗标准方案失败的晚期结直肠癌患者具有潜在的临床获益，安全性事件总体可控，出现高血压的患者可能伴随了较好的预后。

Efficacy and safety of apatinib in the further line treatment for patients with advanced colorectal cancer failed after standard therapy and the preliminary analysis of efficacy predictors

AIM: To investigate the efficacy and safety of apatinib monotherapy in the third line and further line treatment for patients with advanced colorectal cancer failed after standard therapy and the preliminary analysis of efficacy predictors. METHODS: The required sample size in this study was calculated with the PASS 15.0 software. Advanced colorectal cancer patients failed after standard therapy from May 2017 to October 2018 were included in this study. Patients enrolled in this study were given apatinib either 750 mg or 500 mg monotherapy. The objective remission rate (ORR) and disease control rate (DCR) were evaluated after 2 cycles treatment. The progression-free survival (PFS) and overall survival (OS) were evaluated at the follow-up period, and adverse events during treatment were recorded. The prognosis of patients with or without hypertension was analyzed. The primary endpoint of this study was PFS, and second endpoint was ORR, DCR, OS, safety evaluation and efficacy predictor analysis.RESULTS: Of the 51 patients included, 45 patients were available for efficacy and safety evaluation. Of the 45 advanced colorectal cancer received apatinib monotherapy, the objective response rate (ORR) was 11.11%, and the DCR was 77.78%, the median PFS was 3.95 months, the median OS was 10.3 months. And the common adverse reactions were hypertension, hand-foot syndrome, proteinuria and diarrhea. And the adverse reactions above grade 3 with higher incidence were hand-foot syndrome 6 cases (13.33%), hypertension 5 cases (11.11%), proteinuria 3 cases (6.67%) and diarrhea 3 cases (6.67%). PFS of patients with hypertension was significantly longer than that of patients without hypertension, which was statistical difference (P=0.01). CONCLUSION: Patients with advanced colorectal cancer failed the standard therapy and received apatinib treatment had potential clinical benefits, and the overall toxicity profile was manageable. Patients with hypertension might confer a better prognosis.