Predictive factors for first dose reduction and interruption of lenvatinib after beginning of the standard dose in Japanese patients with thyroid cancer.

Autor: Fujita K; Department of Pharmacy, Akita University Hospital, Akita, Japan., Nagahama M; Department of Surgery, Ito Hospital, Tokyo, Japan., Suzuki A; Department of Surgery, Ito Hospital, Tokyo, Japan., Masaki C; Department of Surgery, Ito Hospital, Tokyo, Japan., Sugino K; Department of Surgery, Ito Hospital, Tokyo, Japan., Ito K; Department of Surgery, Ito Hospital, Tokyo, Japan., Miura M; Department of Pharmacy, Akita University Hospital, Akita, Japan. m-miura@hos.akita-u.ac.jp.; Department of Pharmacokinetics, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan. m-miura@hos.akita-u.ac.jp.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2024 Dec 19; Vol. 95 (1), pp. 8. Date of Electronic Publication: 2024 Dec 19.
DOI: 10.1007/s00280-024-04729-6
Abstrakt: Purpose: The associations between first dose reduction or interruption by side effects and lenvatinib plasma trough concentration (C 0 ) after administration of a starting dose of 24 mg in 70 Japanese patients with thyroid cancer were evaluated.
Methods: Plasma samples were collected each week for 1 month and at the first incidence of side effects leading to dose reduction or interruption after beginning administration of 24 mg lenvatinib.
Results: The area under the receiver operating characteristic curve was 0.789 at a lenvatinib C 0 threshold of 128.25 ng/mL for predicting the first dose reduction or interruption. The median time to the first dose reduction or interruption was 14.0 days in patients with a C 0 of ≥ 128.25 ng/mL and 21.0 days in those with a C 0 of < 128.25 ng/mL (P = 0.001). At one, two, three and four weeks respectively, the first dose reduction or interruption was associated with body weight (P = 0.034); sex (P = 0.021); sex, age, and lenvatinib C 0 of ≥ 128.25 ng/mL (P = 0.025, 0.024, and 0.048, respectively); and age and lenvatinib C 0 of ≥ 128.25 ng/mL (each P = 0.004).
Conclusions: On day 8 after administration of 24 mg lenvatinib, lenvatinib dose may be adjusted based on the target C 0 of 128.25 ng/mL to maintain a high dose intensity during this early phase; however, because persistence of a higher C 0 of 128.25 ng/mL causes early dose interruption or reduction, prospective dose reduction based on the next lower target C 0 for the maintenance phase may be necessary.
Competing Interests: Declarations. Conflict of interest: All authors have no conflicts of interest. The authors declare no competing interests. Research involving human participants: The study was performed in accordance with the ethical standards of the Declaration of Helsinki and its subsequent amendments. Informed consent: Signed informed consent was obtained from all patients.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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