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Open Access 22-03-2024 | Regorafenib | Research

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

Authors: Kazuma Fujita, Daiki Taguchi, Koji Fukuda, Taichi Yoshida, Kazuhiro Shimazu, Hanae Shinozaki, Hiroyuki Shibata, Masatomo Miura

Published in: Investigational New Drugs

Summary

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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Title: 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
Authors: Kazuma Fujita
Daiki Taguchi
Koji Fukuda
Taichi Yoshida
Kazuhiro Shimazu
Hanae Shinozaki
Hiroyuki Shibata
Masatomo Miura
Publication date: 22-03-2024
Publisher: Springer US
Keywords: Regorafenib
Colorectal Cancer
Colorectal Cancer
Gastrointestinal Stromal Tumor
Published in: Investigational New Drugs
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-024-01429-z

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