Phase 1 dose-finding and pharmacokinetic study of eribulin-liposomal formulation in patients with solid tumours.
Dean, Emma J
AffiliationBeatson West of Scotland Cancer Centre, Glasgow, UK
MetadataShow full item record
AbstractBACKGROUND: 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.
CitationEvans 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.
JournalBritish Journal of Cancer
- A phase 1b/2, open-label, dose-escalation, and dose-confirmation study of eribulin mesilate in combination with capecitabine.
- Authors: Twelves C, Anthoney A, Savulsky CI, Guo M, Reyderman L, Cresti N, Semiglazov V, Timcheva C, Zubairi I, Morrison R, Plummer R, Evans TRJ
- Issue date: 2019 Mar
- Phase I study of the halichondrin B analogue eribulin mesylate in combination with cisplatin in advanced solid tumors.
- Authors: Koczywas M, Frankel PH, Synold TW, Lenz HJ, Mortimer JE, El-Khoueiry AB, Gandara DR, Cristea MC, Chung VM, Lim D, Reckamp KL, Lau DH, Doyle LA, Ruel C, Carroll MI, Newman EM
- Issue date: 2014 Dec 9
- Phase I study of eribulin mesylate administered once every 21 days in patients with advanced solid tumors.
- Authors: Tan AR, Rubin EH, Walton DC, Shuster DE, Wong YN, Fang F, Ashworth S, Rosen LS
- Issue date: 2009 Jun 15
- A phase 1 study of eribulin mesylate (E7389), a novel microtubule-targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314).
- Authors: Schafer ES, Rau RE, Berg S, Liu X, Minard CG, D'Adamo D, Scott R, Reyderman L, Martinez G, Devarajan S, Reid JM, Fox E, Weigel BJ, Blaney SM
- Issue date: 2018 Aug
- A phase I study of eribulin mesylate (E7389), a mechanistically novel inhibitor of microtubule dynamics, in patients with advanced solid malignancies.
- Authors: Goel S, Mita AC, Mita M, Rowinsky EK, Chu QS, Wong N, Desjardins C, Fang F, Jansen M, Shuster DE, Mani S, Takimoto CH
- Issue date: 2009 Jun 15