Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours.
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Embargo End Date
ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2019-02-19
Date Accepted
2019-01-03
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.
Citation
British journal of cancer, 2019, 120 (4), pp. 379 - 386
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
0007-0920
eISSN
1532-1827
Collections
Research Team
Medicine (de Bono Prostate)