Predictive factors for first dose reduction and interruption of lenvatinib after beginning of the standard dose in Japanese patients with thyroid cancer.
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引用次数: 0
Abstract
Purpose: The associations between first dose reduction or interruption by side effects and lenvatinib plasma trough concentration (C0) 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 C0 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 C0 of ≥ 128.25 ng/mL and 21.0 days in those with a C0 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 C0 of ≥ 128.25 ng/mL (P = 0.025, 0.024, and 0.048, respectively); and age and lenvatinib C0 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 C0 of 128.25 ng/mL to maintain a high dose intensity during this early phase; however, because persistence of a higher C0 of 128.25 ng/mL causes early dose interruption or reduction, prospective dose reduction based on the next lower target C0 for the maintenance phase may be necessary.
期刊介绍:
Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.