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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2012

01-12-2012 | Original Article

Pharmacokinetics of eribulin mesylate in patients with solid tumors and hepatic impairment

Authors: L. A. Devriese, P. O. Witteveen, S. Marchetti, M. Mergui-Roelvink, L. Reyderman, J. Wanders, A. Jenner, G. Edwards, J. H. Beijnen, E. E. Voest, J. H. M. Schellens

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2012

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Abstract

Purpose

The aim of this study was to determine the plasma pharmacokinetics of eribulin mesylate in patients with solid tumors with mild and moderate hepatic impairment.

Patients and methods

A phase I, pharmacokinetic study was performed in patients with advanced solid tumors and normal hepatic function or Child-Pugh A (mild) or Child-Pugh B (moderate) hepatic impairment. Treatments were given on day 1 and 8 of a 21-day cycle and consisted of 1.4, 1.1 and 0.7 mg/m2 eribulin mesylate, for normal hepatic function, Child-Pugh A and B hepatic impairment, respectively. Also safety and anti-tumor activity were determined.

Results

Hepatic impairment increased exposure to eribulin. In patients with Child-Pugh A (N = 7) and Child-Pugh B (N = 5), mean dose-normalized AUC0–∞ was 1.75-fold (90 % confidence intervals (CI): 1.16–2.65) and 2.48-fold (90 % CI: 1.57–3.92) increased, respectively, compared with patients who have normal function (N = 6). The most frequently reported treatment-related events were alopecia (12/18) and fatigue (7/18) and these were observed across all groups. Nine patients (50 %) had stable disease as best response.

Conclusions

A reduced dose of 1.1 and 0.7 mg/m2 of eribulin mesylate is recommended for patients with Child-Pugh A or B hepatic impairment, respectively.
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Metadata
Title
Pharmacokinetics of eribulin mesylate in patients with solid tumors and hepatic impairment
Authors
L. A. Devriese
P. O. Witteveen
S. Marchetti
M. Mergui-Roelvink
L. Reyderman
J. Wanders
A. Jenner
G. Edwards
J. H. Beijnen
E. E. Voest
J. H. M. Schellens
Publication date
01-12-2012
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-012-1976-x

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