Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours.
Authors
Evans, TDean, Emma J
Molife, L
Lopez, J
Ranson, M
El-Khouly, F
Zubairi, I
Savulsky, C
Reyderman, L
Jia, Y
Sweeting, L
Greystoke, A
Barriuso, Jorge
Kristeleit, R
Affiliation
Beatson West of Scotland Cancer Centre, Glasgow, UKIssue Date
2019
Metadata
Show full item recordAbstract
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.Citation
Evans TRJ, Dean E, Molife LR, Lopez J, Ranson M, El-Khouly F, et al. Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours. Br J Cancer. 2019 Jan 25.Journal
British Journal of CancerDOI
10.1038/s41416-019-0377-xPubMed ID
30679780Additional Links
https://dx.doi.org/10.1038/s41416-019-0377-xType
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41416-019-0377-x