Fujii Hironori, Tsuchiya Masami, Watanabe Daichi, Chin Miki, Hirate Daisuke, Takahashi Katsuyuki, Go Makiko, Kudo Toshihiro, Shimomura Kazuhiro, Ando Yosuke, Tani Shinya, Takahashi Takao, Hayashi Katsuhisa, Hashimoto Hironobu, Matsunami Naomi, Takahashi Masaya, Hasegawa Akiko, Uchida Takashi, Kubo Akiko, Matsuhashi Nobuhisa, Suzuki Akio, Nishimura Junichi, Inui Naoki, Iihara Hirotoshi
Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
Department of Pharmacy, Miyagi Cancer Center, Miyagi, Japan.
Support Care Cancer. 2025 May 13;33(6):469. doi: 10.1007/s00520-025-09504-8.
Although the efficacy of trifluridine/tipiracil hydrochloride (TAS-102) in treating metastatic colorectal cancer (mCRC) is well established, its non-hematologic toxicities in relation to renal function remain unclear. This study aimed to assess the impact of creatinine clearance (Ccr) on non-hematologic toxicities, including nausea and vomiting, in patients with mCRC treated with TAS-102.
This study was conducted as a post-hoc analysis of the JASCC-CINV2001 study, a multicenter observational study of mCRC patients. Using a Cox proportional hazards model, we assessed the relationship between Ccr and nausea or vomiting, and used a generalized estimating equations (GEE) logistic regression model to analyze the association between Ccr and additional toxicities, including fatigue, constipation, diarrhea, insomnia, and dysgeusia. Toxicities were evaluated at weekly intervals over four weeks.
Among 100 patients, median Ccr was 80.5 ml/min. The primary analysis showed no significant association between Ccr and nausea or vomiting. However, the secondary analysis revealed a significant link between lower Ccr and the incidence of diarrhea (P = 0.02).
These results suggest that although TAS-102-induced nausea and vomiting are not strongly influenced by renal function, decreased renal function increases the risk of diarrhea. Enhanced antiemetic measures may not be necessary for TAS-102 patients with impaired renal function, but monitoring for diarrhea is recommended.
尽管曲氟尿苷/盐酸替匹嘧啶（TAS-102）治疗转移性结直肠癌（mCRC）的疗效已得到充分证实，但其与肾功能相关的非血液学毒性仍不明确。本研究旨在评估肌酐清除率（Ccr）对接受TAS-102治疗的mCRC患者非血液学毒性（包括恶心和呕吐）的影响。
本研究作为JASCC-CINV2001研究的事后分析进行，该研究是一项针对mCRC患者的多中心观察性研究。我们使用Cox比例风险模型评估Ccr与恶心或呕吐之间的关系，并使用广义估计方程（GEE）逻辑回归模型分析Ccr与其他毒性（包括疲劳、便秘、腹泻、失眠和味觉障碍）之间的关联。在四周内每周评估一次毒性。
100例患者中，Ccr中位数为80.5 ml/min。初步分析显示Ccr与恶心或呕吐之间无显著关联。然而，二次分析显示较低的Ccr与腹泻发生率之间存在显著关联（P = 0.02）。
这些结果表明，尽管TAS-102引起的恶心和呕吐不受肾功能的强烈影响，但肾功能下降会增加腹泻风险。对于肾功能受损的TAS-102患者，可能无需加强止吐措施，但建议监测腹泻情况。
