Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba City, Ibaraki, 305-8575, Japan.
Division of Cancer Immunology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa city, Chiba, Japan.
Sci Rep. 2023 Oct 20;13(1):17931. doi: 10.1038/s41598-023-45244-7.
Renal impairment may be associated with an increased risk of hematologic events (AEs) in patients undergoing treatment with trifluridine/tipiracil (FTD/TPI). This study aimed to investigate the specific types of AEs linked to renal impairment in patients with metastatic colorectal cancer (mCRC) receiving FTD/TPI, using real-world data. Among the patients included in the REGOTAS study (a retrospective study of FTD/TPI versus regorafenib), those treated with FTD/TPI were evaluated. Creatinine clearance values of < 30, 30-60, 60-90, and > 90 mL/min were defined as severe, moderate, mild renal impairment, and normal renal function, respectively. Renal impairment was analyzed as a risk factor for grade 3 or higher AEs using a logistic regression model. Overall survival (OS) and progression-free survival (PFS) based on renal impairment were evaluated. A total of 309 patients were included in the analysis, with 124, 130, and 55 patients divided into the normal, mild, and moderate-to-severe groups, respectively. The risk of grade 3 or higher neutropenia was significantly higher in the moderate-to-severe group (odds ratio 3.47; 95% confidence interval 1.45-8.30; P = 0.005), but there was no significant increase in the risk of non-hematologic AEs in any of the groups. The OS and PFS of patients in the mild and moderate-to-severe groups were comparable to those in the normal group. Patients with mCRC and moderate/severe renal impairment receiving FTD/TPI therapy may develop severe neutropenia; however, FTD/TPI remains a viable treatment option due to its clinical benefit.
肾功能损害可能与接受三氟尿苷/替匹嘧啶(FTD/TPI)治疗的患者发生血液学不良事件(AEs)的风险增加相关。本研究旨在使用真实世界数据,探讨转移性结直肠癌(mCRC)患者接受 FTD/TPI 治疗时与肾功能损害相关的特定类型 AEs。在 REGOTAS 研究(一项 FTD/TPI 与regorafenib 对比的回顾性研究)中纳入的患者中,评估了接受 FTD/TPI 治疗的患者。定义肌酐清除率<30、30-60、60-90 和>90 mL/min 分别为严重、中度、轻度肾功能损害和正常肾功能。使用逻辑回归模型分析肾功能损害作为 3 级或更高 AEs 的危险因素。根据肾功能损害评估总生存期(OS)和无进展生存期(PFS)。共纳入 309 例患者,其中 124、130 和 55 例患者分别分为正常、轻度和中重度组。中重度组 3 级或更高中性粒细胞减少症的风险显著增加(优势比 3.47;95%置信区间 1.45-8.30;P=0.005),但任何组中非血液学 AEs 的风险均无显著增加。轻度和中重度组患者的 OS 和 PFS 与正常组相当。接受 FTD/TPI 治疗的 mCRC 且伴有中重度肾功能损害的患者可能发生严重中性粒细胞减少症;然而,由于其临床获益,FTD/TPI 仍然是一种可行的治疗选择。