1. Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours.
- Author
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Evans, T. R. Jeffry, Dean, Emma, Molife, L. Rhoda, Lopez, Juanita, Ranson, Malcolm, El-Khouly, Fatima, Zubairi, Ishtiaq, Savulsky, Claudio, Reyderman, Larisa, Jia, Yan, Sweeting, Lorna, Greystoke, Alastair, Barriuso, Jorge, and Kristeleit, Rebecca
- Subjects
COMPARATIVE studies ,DRUG dosage ,DOSAGE forms of drugs ,DRUG toxicity ,HETEROCYCLIC compounds ,KETONES ,RESEARCH methodology ,MEDICAL cooperation ,ARTIFICIAL membranes ,RESEARCH ,RESEARCH funding ,TUMORS ,EVALUATION research - 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. [ABSTRACT FROM AUTHOR]- Published
- 2019
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