瑞戈非尼联合每两周一次的曲氟尿苷/替匹嘧啶治疗难治性转移性结直肠癌的疗效和安全性：一项多中心单臂II期试验。
Efficacy and safety of regorafenib plus biweekly trifluridine/tipiracil for refractory metastatic colorectal cancer: a multicenter single-arm phase II trial.
作者信息
Wang Xiangling, Li Zhen, Sha Dan, Ren Haipeng, Yi Cuihua, Li Shuguang, Wang Peng, Chu Yunxia, Li Changlun, Shan Guanglian, Wang Jian, Yang Xiaorong, Hao Jing
机构信息
Department of Medical Oncology, Qilu Hospital of Shandong University, Jinan 250012, People's Republic of China.
Department of Medical Oncology, Linyi Cancer Hospital, Linyi, People's Republic of China.
出版信息
Oncologist. 2025 Jun 4;30(6). doi: 10.1093/oncolo/oyaf129.
BACKGROUND
Both regorafenib and trifluridine/tipiracil (TAS-102) monotherapies have shown significant but limited survival benefits in metastatic colorectal cancer (mCRC) cases who progress after standard treatments. This study aimed to evaluate the efficacy and safety of regorafenib plus biweekly TAS-102 in refractory mCRC.
METHODS
In this single-arm multicenter phase II trial (ChiCTR2300071752), eligible patients received regorafenib at 120 mg/day for 21 days in a 4-week cycle or were treated with a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day). TAS-102 was administered biweekly (30 mg/m2 bid on days 1-5). The primary endpoint was progression-free survival (PFS). The secondary endpoints included safety, response rate (ORR), disease control rate (DCR), and overall survival (OS).
RESULTS
Between March 1, 2022 and December 1, 2023, 28 patients were enrolled. Totally 24 patients had at least one response evaluation. Median PFS and OS were 4.9 months (95% CI, 4.2-5.6) and 15.4 months (95% CI, 11.1-19.7). The ORR was 8.3% and the DCR was 83.3%. Grade 3 or 4 treatment-related adverse events occurred in 21.4% of patients, including hypertension (7.1%), neutropenia (7.1%), thrombocytopenia (3.6%), and hoarseness (3.6%).
CONCLUSIONS
Regorafenib plus biweekly TAS-102 showed promising benefits in refractory mCRC cases, and adverse events were generally tolerable and manageable.
DISCUSSION
(ClinicalTrials.gov Identifier: ChiCTR2300071752. IRB Approved: KYLL-202203-026-1.).
背景
regorafenib和曲氟尿苷/替匹嘧啶（TAS-102）单药治疗在标准治疗后进展的转移性结直肠癌（mCRC）患者中均显示出显著但有限的生存获益。本研究旨在评估regorafenib联合每两周一次的TAS-102治疗难治性mCRC的疗效和安全性。
方法
在这项单臂多中心II期试验（ChiCTR2300071752）中，符合条件的患者接受regorafenib，剂量为120mg/天，每4周为一个周期，持续21天，或采用剂量递增策略（80mg/天，随后每周增加40mg至120mg/天）。TAS-102每两周给药一次（第1 - 5天30mg/m²，每日两次）。主要终点是无进展生存期（PFS）。次要终点包括安全性、缓解率（ORR）、疾病控制率（DCR）和总生存期（OS）。
结果
在2022年3月1日至2023年12月1日期间，共纳入28例患者。共有24例患者进行了至少一次缓解评估。中位PFS和OS分别为4.9个月（95%CI，4.2 - 5.6）和15.4个月（95%CI，11.1 - 19.7）。ORR为8.3%，DCR为83.3%。21.4%的患者发生3级或4级治疗相关不良事件，包括高血压（7.1%）、中性粒细胞减少（7.1%）、血小板减少（3.6%）和声音嘶哑（3.6%）。
结论
regorafenib联合每两周一次的TAS-102在难治性mCRC患者中显示出有前景的获益，且不良事件通常可耐受和可控。
讨论
（ClinicalTrials.gov标识符：ChiCTR2300071752。机构审查委员会批准：KYLL-202203-026-1。）
Zotero 插件