70ORelationships between lenvatinib plasma concentration and toxicity in Japanese cancer patients
Annals of Oncology(2018)
摘要
Background: Lenvatinib is an oral, multi-targeting inhibitor for VEGFR, FGFR, PDGFR, KIT and RET. This agent has been approved for thyroid cancer with a recommended dosage of 24-mg QD and for hepato-cellular carcinoma with 8 or 12-mg QD. Although lenvatinib has substantial anti-tumor activity for thyroid cancer as well as other solid tumors including colorectal cancer and non-small cell lung cancer, dose modification is frequently required due to proteinuria, decreased weight, anorexia, hand-foot syndrome and some other gastro-intestinal toxicities. Dose individualization with close plasma concentration monitoring could contribute to address these issues in routine clinical practice. Methods: Patients, who received lenvatinib as practical treatment setting, were enrolled in our prospective pharmacokinetic individualized study. Plasma trough concentration as well as dried plasma spot (DPS) samples were obtained from all enrolled patients. Lenvatinib plasma concentrations were measured by in-house LC/MS/MS, and investigated with the correlation with toxicities by lenvatinib. The study protocol was approved by our institutional review board and informed consent was obtained from all patients. Results: From Jun 2017 to Jun 2018, 17 patients (13 thymic cancer, 1 thyroid cancer and 3 lung cancer with RET-fusion) were enrolled. At a dosage of 24-mg QD, the geometric mean plasma lenvatinib trough concentrations at steady state was averaged at 65.1 (range 39.3-105.4) ng/mL. All enrolled patients had required a dose reduction due to AEs, and final lenvatinib doses with acceptable tolerability were 20 mg in 3, 14 mg in 5, 10 mg in 4, 8 mg in 3, and 4 mg in 2 patients, respectively. The geometric mean plasma lenvatinib trough concentrations with final dosage was 52.6 (range 25.8-107.4) ng/mL. All DPS samples showed comparable concentrations to plasma samples. Conclusions: The plasma lenvatinib trough concentration with final dosage adjusted by AEs was < 60 ng/mL. Therapeutic drug monitoring of lenvatinib could minimize unacceptable AEs and contribute individualized dosing. Also, we firstly confirmed the feasibility of lenvatinib DPS assay with high compatibility with plasma concentrations. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: N. Yamamoto, Y. Fujiwara: Eisai Co., Ltd. All other authors have declared no conflicts of interest.
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关键词
lenvatinib plasma concentration,cancer,toxicity
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