Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours

Evans, T.R. J. et al. (2019) Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours. British Journal of Cancer, (doi: 10.1038/s41416-019-0377-x)

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Abstract

Background: This phase 1 study examined the safety, tolerability, pharmacokinetics and preliminary efficacy of eribulin-liposomal formulation (eribulin-LF) in patients with advanced solid tumours. Methods: Eligible patients with ECOG PS 0–1 were treated with eribulin-LF either on day 1 every 21 days (Schedule 1), or on days 1 and 15 every 28 days (Schedule 2). Doses ranged from 1.0 to 3.5 mg/m2, with dose escalation in a 3 + 3 design. The dose-expansion phase evaluated eribulin-LF in select tumour types. Primary objectives: maximum tolerated dose (MTD) and the recommended dose/schedule of eribulin-LF. Results: Totally, 58 patients were enroled (median age = 62 years). The MTD was 1.4 mg/m2 (Schedule 1) or 1.5 mg/m2 (Schedule 2), the latter dose selected for the dose-expansion phase. Dose-limiting toxicity (DLTs) in Schedule 1: hypophosphatemia and increased transaminase levels. DLTs in Schedule 2: stomatitis, increased alanine aminotransferase, neutropenia and febrile neutropenia. The pharmacokinetic profile of eribulin-LF showed a similar half-life to that of eribulin (~30 h), but with a 5-fold greater maximum serum concentration and a 40-fold greater area-under-the-curve. Eribulin-LF demonstrated clinical activity with approximately 10% of patients in both schedules achieving partial responses. Conclusions: Eribulin-LF was well tolerated with a favourable pharmacokinetic profile. Preliminary evidence of clinical activity in solid tumours was observed.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sweeting, Miss Lorna and Evans, Professor Jeff
Authors: Evans, T.R. J., Dean, E., Molife, L. R., Lopez, J., Ranson, M., El-Khouly, F., Zubairi, I., Savulsky, C., Reyderman, L., Jia, Y., Sweeting, L., Greystroke, A., Barriuso, J., and Kristeleit, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Cancer
Publisher:Nature Publishing Group
ISSN:0007-0920
ISSN (Online):1532-1827
Published Online:25 January 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in British Journal of Cancer 2019
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
750721Glasgow ECMCThomas EvansCancer Research UK (CRUK)C58789/A25174ICS - EXPERIMENTAL THERAPEUTICS