A phase 1b/2, open-label, dose-escalation, and dose-confirmation study of eribulin mesilate in combination with capecitabine

Twelves, C. et al. (2019) A phase 1b/2, open-label, dose-escalation, and dose-confirmation study of eribulin mesilate in combination with capecitabine. British Journal of Cancer, 120(6), pp. 579-586. (doi: 10.1038/s41416-018-0366-5) (PMID:30783204) (PMCID:PMC6461928)

Abstract

Background: Capecitabine and eribulin are widely used as single agents in metastatic breast cancer (MBC) and have nonoverlapping toxicities. Methods: In phase 1b (dose escalation), patients with advanced, treatment-refractory, solid tumours received eribulin mesilate intravenously in 21-day cycles according to schedule 1 (day 1) or schedule 2 (days 1, 8) with twice-daily oral capecitabine (1000 mg/m2 days 1–14). In phase 2 (dose confirmation), women with advanced/MBC and ≤3 prior chemotherapies received eribulin mesilate at the maximum tolerated dose (MTD) per the preferred schedule plus capecitabine. Primary objectives were MTD and dose-limiting toxicities (DLTs; phase 1b) and objective response rate (ORR; phase 2). Secondary objectives included progression-free survival (PFS), safety, and pharmacokinetics. Results: DLTs occurred in 4/19 patients (schedule 1) and 2/15 patients (schedule 2). Eribulin pharmacokinetics were dose proportional, irrespective of schedule or capecitabine coadministration. The MTD of eribulin was 1.6 mg/m2 day 1 for schedule 1 and 1.4 mg/m2 days 1 and 8 for schedule 2. ORR in phase 2 (eribulin 1.4 mg/m2 days 1, 8 plus capecitabine) was 43% and median PFS 7.2 months. The most common treatment-related adverse events were neutropenia, leukopenia, alopecia, nausea, and lethargy. Conclusions: The combination of capecitabine and eribulin showed promising efficacy with manageable tolerability in patients with MBC.

• Item Type: Articles
• Additional Information: This work was supported by Eisai Ltd, UK, and by the NIHR Leeds Clinical Research Facility.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Evans, Professor Jeff
• Authors: Twelves, C., Anthoney, A., Savulsky, C. I., Guo, M., Reyderman, L., Cresti, N., Semiglazov, V., Timcheva, C., Zubairi, I., Morrison, R., Plummer, R., and Evans, T.R. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: British Journal of Cancer
• Publisher: Springer Nature
• ISSN: 0007-0920
• ISSN (Online): 1532-1827
• Published Online: 20 February 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in British Journal of Cancer 120(6): 579-586
• Publisher Policy: Reproduced under a Creative Commons License