日本患者白蛋白-胆红素分级与瑞戈非尼及其代谢物M-2和M-5稳态血浆谷浓度之间的关系。

IF 3 3区 医学 Q2 ONCOLOGY Investigational New Drugs Pub Date : 2024-06-01 Epub Date: 2024-03-22 DOI:10.1007/s10637-024-01429-z
Kazuma Fujita, Daiki Taguchi, Koji Fukuda, Taichi Yoshida, Kazuhiro Shimazu, Hanae Shinozaki, Hiroyuki Shibata, Masatomo Miura
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摘要

本研究旨在确定21名接受瑞戈非尼治疗的患者体内瑞戈非尼及其代谢物(N-氧化物代谢物(M-2)和去甲基N-氧化物代谢物(M-5))的血浆谷浓度(C0)是否受白蛋白-胆红素(ALBI)分级的影响。瑞戈非尼的用药剂量为 40 至 160 毫克,每天一次,以 3 周为一个用药周期,1 周为一个停药周期。治疗开始后第8天,采用高效液相色谱法测定瑞戈非尼及其主要代谢物的C0值。与1级患者相比,ALBI 2级患者的瑞戈非尼及其代谢物M-2和M-5的C0值明显降低(P=0.023、0.003和0.017)。1级ALBI患者体内瑞戈非尼及其代谢物的总C0明显高于2级患者(3.489 μg/mL vs. 1.48 μg/mL;P = 0.009)。ALBI2级患者的中位相对剂量强度(RDI)明显低于1级患者(21.9% vs. 62.9%;P = 0.006)。在21名结直肠癌患者中的15名患者中,ALBI 2级患者(n = 9)的中位总生存时间明显短于1级患者(n = 6;P = 0.013)。对ALBI 2级患者施用低剂量瑞戈非尼会降低瑞戈非尼的RDI,降低疗效,因为瑞戈非尼无法维持适当的C0。有必要定期监测瑞戈非尼的C0,以指导剂量调整。
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Association between albumin-bilirubin grade and plasma trough concentrations of regorafenib and its metabolites M-2 and M-5 at steady-state in Japanese patients.

The aim of the present study was to determine whether the trough plasma concentrations (C0) of regorafenib and its metabolites, the N-oxide metabolite (M-2) and the desmethyl N-oxide metabolite (M-5), in 21 patients receiving regorafenib therapy were affected by albumin-bilirubin (ALBI) grade. Regorafenib was administered at dosages ranging from 40 to 160 mg once daily on a 3-week-on, 1-week-off cycle. C0 values of regorafenib and its major metabolites were measured by high-performance liquid chromatography on day 8 after treatment initiation. The C0 values of regorafenib and metabolites M-2 and M-5 were significantly lower in patients with ALBI grade 2 as compared with grade 1 (P = 0.023, 0.003 and 0.017, respectively). The total C0 of regorafenib and its metabolites was significantly higher in ALBI grade 1 patients relative to grade 2 (3.489 μg/mL vs. 1.48 μg/mL; P = 0.009). The median relative dose intensity (RDI) of patients categorized as ALBI grade 2 was significantly lower than that of grade 1 patients (21.9% vs. 62.9%; P = 0.006). In 15 colorectal cancer patients among the total 21 patients, patients with ALBI grade 2 (n = 9) had a significantly shorter median overall survival time than patients with grade 1 (n = 6; P = 0.013). Administering a low dose of regorafenib to patients with ALBI grade 2 reduces the RDI of regorafenib and lowers treatment efficacy, as an appropriate C0 of regorafenib is not maintained. Monitoring the C0 of regorafenib regularly is necessary to guide dose adjustment.

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来源期刊
CiteScore
7.60
自引率
0.00%
发文量
121
审稿时长
1 months
期刊介绍: The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.
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