阿帕替尼联合5-氟尿嘧啶作为转移性结直肠癌三线或后续治疗方案：一项II期单臂前瞻性研究。
Apatinib plus 5-fluorouracil as a third or subsequent-line treatment option for metastatic colorectal cancer: a phase-II, single-arm, prospective study.
作者信息
Chen Runzhi, Yang Liu, Hu Sheng, Yin Zhusheng, Nie Yanli, Xu Hongli, Zhong Yi, Zhu Yuze, Liang Xinjun, Xu Huiting
机构信息
Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Ann Transl Med. 2022 Jan;10(2):100. doi: 10.21037/atm-22-77.
BACKGROUND
For metastatic colorectal cancer (mCRC) patients for whom at least 2 lines of previous standard therapies have failed, the prognosis is often unfavorable due to very limited subsequent treatment options. We sought to explore the efficacy of apatinib, an oral small-molecule vascular endothelial growth factor receptor-2 inhibitor, plus 5-fluorouracil (5-FU) as a third- or subsequent-line treatment for mCRC.
METHODS
In this phase-II, single-arm, prospective study, the eligible patients had been histologically confirmed to have adenocarcinoma of the colon or rectum for which at least 2 previous regimens of standard therapies had failed. All the patients were treated with a daily dose of 250 mg of apatinib, in combination with capecitabine, Tegafur Gimeracil Oteracil Potassium Capsule (S-1), or 5-FU, until disease progression, unacceptable toxicity, or consent withdrawal.
RESULTS
From June 2017 to April 2018, 16 patients were enrolled in this study. Among them, 4 achieved partial response, 7 had stable disease, and 5 had progression disease, resulting in an objective response rate of 25.00% [95% confidence interval (CI): 7.27-52.38%], and a disease control rate of 68.75% (95% CI: 41.34-88.98%). The median progression-free survival (PFS) was 4.83 months (95% CI: 2.17-8.90 months), and the median overall survival (OS) was 9.10 months (95% CI: 5.59-15.18 months). The common treatment-related adverse events (AEs) were hand-foot syndrome (56.25%), hypertension (37.50%), proteinuria (37.50%), gingival bleeding (18.75%) and abdominal pain (18.75%). Grade 3 AEs, including hand-foot syndrome (18.75%), hypertension (12.50%), and proteinuria (12.50%), were observed in 7 patients.
CONCLUSIONS
The combination regimen of apatinib plus 5-FU had encouraging anti-tumor efficacy, and is a feasible third- or subsequent-line treatment option for mCRC.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03210064.
背景
对于既往至少2线标准治疗失败的转移性结直肠癌（mCRC）患者，由于后续治疗选择非常有限，预后往往不佳。我们试图探索阿帕替尼（一种口服小分子血管内皮生长因子受体-2抑制剂）联合5-氟尿嘧啶（5-FU）作为mCRC三线或后续治疗的疗效。
方法
在这项II期单臂前瞻性研究中，符合条件的患者经组织学确诊为结肠或直肠癌，且既往至少2种标准治疗方案失败。所有患者每日服用250 mg阿帕替尼，联合卡培他滨、替吉奥胶囊（S-1）或5-FU，直至疾病进展、出现不可接受的毒性或患者撤回同意书。
结果
2017年6月至2018年4月，16例患者纳入本研究。其中，4例达到部分缓解，7例疾病稳定，5例疾病进展，客观缓解率为25.00%[95%置信区间（CI）：7.27-52.38%]，疾病控制率为68.75%（95%CI：41.34-88.98%）。中位无进展生存期（PFS）为4.83个月（95%CI：2.17-8.90个月），中位总生存期（OS）为9.10个月（CI：5.59-15.18个月）。常见的治疗相关不良事件（AE）为手足综合征（56.25%）、高血压（37.50%）、蛋白尿（37.50%）、牙龈出血（18.75%）和腹痛（18.75%）。7例患者出现3级AE，包括手足综合征（18.75%）、高血压（12.50%）和蛋白尿（12.50%）。
结论
阿帕替尼联合5-FU的联合方案具有令人鼓舞的抗肿瘤疗效，是mCRC可行的三线或后续治疗选择。
试验注册
ClinicalTrials.gov标识符：NCT03210064。
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