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

Evans, TRJ; Dean, E; Molife, LR; Lopez, J; Ranson, M; El-Khouly, F; Zubairi, I; ... Kristeleit, R; + view all (2019) Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours. British Journal of Cancer , 120 pp. 379-386. 10.1038/s41416-019-0377-x. Green open access

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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.

Type: Article
Title: Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41416-019-0377-x
Publisher version: https://doi.org/10.1038/s41416-019-0377-x
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/10068274
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