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

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.