Dai Yuhong, Sun Li, Zhuang Liang, Zhang Mingsheng, Zou Yanmei, Yuan Xianglin, Qiu Hong
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Gastrointest Oncol. 2022 Apr;13(2):722-731. doi: 10.21037/jgo-22-285.
At present, regorafenib and fruquintinib are the standard regimens for refractory metastatic colorectal cancer patients in China, but both options have limited efficacy. The aim of this study was to investigate the efficacy and safety of low-dose apatinib plus S-1 compared with regorafenib and fruquintinib in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies.
The records of 114 patients with refractory mCRC in our center from April 2016 to September 2020 were retrospectively reviewed. Among these patients, 43 received apatinib 250 mg/day combined with S-1, 36 received regorafenib starting at 80 mg/day with weekly escalation, and 35 received fruquintinib 5 mg/day orally. Patients received radiographic examination every 1.5-2 months during the treatment period, progression-free survival time and overall survival time were analyzed and recorded.
The baseline clinical characteristics of the patients were broadly similar among the three groups. The median progression-free survival (mPFS) was 3.9 months [95% confidence interval (CI): 2.5-5.3] in the apatinib plus S-1 group, 3.1 months (95% CI: 1.9-4.2) in the fruquintinib group, and 2.4 months (95% CI: 2.1-2.7) in the regorafenib group, the mPFS of apatinib plus S-1 was significantly longer than that of regorafenib (HR =0.49, P=0.003) and fruquintinib (HR =0.60, P=0.048). The median overall survival (OS) was 8.2 months (95% CI: 5.4-11.0) in the apatinib plus S-1 group, 7.8 months (95% CI: 5.3-10.3) in the fruquintinib group, and 7.5 months (95% CI: 4.2-10.7) in the regorafenib group, which was comparable among the 3 groups. There was no statistical difference in disease control rate (DCR) among the three groups. Patients in the apatinib plus S-1 group had a higher incidence of hematological toxicity including anemia (62.8%), neutropenia (30.2%), and thrombocytopenia (39.5%), and the hand-foot skin reaction (58.3%) was more prevalent in the regorafenib group, while the adverse reaction of hypertension (45.7%) in the fruquintinib group was very significant.
Low-dose apatinib plus S-1 prolonged PFS compared with regorafenib and fruquintinib, and is a potential alternative regimen for the treatment of refractory mCRC with tolerable and controlled toxicity.
目前，瑞戈非尼和呋喹替尼是中国难治性转移性结直肠癌患者的标准治疗方案，但这两种方案的疗效均有限。本研究旨在探讨低剂量阿帕替尼联合S-1与瑞戈非尼和呋喹替尼相比，在标准治疗难治的转移性结直肠癌（mCRC）患者中的疗效和安全性。
回顾性分析了2016年4月至2020年9月在本中心就诊的114例难治性mCRC患者的病历。其中，43例患者接受阿帕替尼250mg/天联合S-1治疗，36例患者接受瑞戈非尼起始剂量80mg/天并每周递增剂量治疗，35例患者接受呋喹替尼5mg/天口服治疗。治疗期间，患者每1.5 - 2个月进行一次影像学检查，分析并记录无进展生存期和总生存期。
三组患者的基线临床特征大致相似。阿帕替尼联合S-1组的中位无进展生存期（mPFS）为3.9个月[95%置信区间（CI）：2.5 - 5.3]，呋喹替尼组为3.1个月（95%CI：1.9 - 4.2），瑞戈非尼组为2.4个月（95%CI：2.1 - 2.7），阿帕替尼联合S-1组的mPFS显著长于瑞戈非尼组（HR =0.49，P =0.003）和呋喹替尼组（HR =0.60，P =0.048）。阿帕替尼联合S-1组的中位总生存期（OS）为8.2个月（95%CI：5.4 - 11.0），呋喹替尼组为7.8个月（95%CI：5.3 - 10.3），瑞戈非尼组为7.5个月（95%CI：4.2 - 10.7），三组之间具有可比性。三组的疾病控制率（DCR）无统计学差异。阿帕替尼联合S-1组患者血液学毒性发生率较高，包括贫血（62.8%）、中性粒细胞减少（30.2%）和血小板减少（39.5%），手足皮肤反应在瑞戈非尼组更为普遍（58.3%），而呋喹替尼组高血压不良反应（45.7%）非常显著。
与瑞戈非尼和呋喹替尼相比，低剂量阿帕替尼联合S-1可延长PFS，是治疗难治性mCRC的一种潜在替代方案，其毒性可耐受且可控。
