Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours.
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Date
2019-02ICR Author
Author
Evans, TRJ
Dean, E
Molife, LR
Lopez, J
Ranson, M
El-Khouly, F
Zubairi, I
Savulsky, C
Reyderman, L
Jia, Y
Sweeting, L
Greystoke, A
Barriuso, J
Kristeleit, R
Type
Journal Article
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.
Collections
Subject
Humans
Neoplasms
Ketones
Furans
Liposomes
Drug Compounding
Maximum Tolerated Dose
Adult
Aged
Middle Aged
Female
Male
Research team
Medicine (de Bono Prostate)
Language
eng
Date accepted
2019-01-03
License start date
2019-02
Citation
British journal of cancer, 2019, 120 (4), pp. 379 - 386