ABSTRACT: The search for cytotoxic agents from marine natural products ultimately led to the production of eribulin, which is a synthetic macrocyclic ketone analog of halichondrin B. Eribulin binds to tubulin to induce mitotic arrest and gained approval in Japan in May 2010; it was approved by the US Food and Drug Administration in November 2010 and the European Medicines Agency in March 2011 and was reimbursed by the Taiwan National Health Insurance in December 2014 for patients with metastatic breast cancer who had received at least one anthracycline and one taxane. The recommended regimen for eribulin mesylate comprises intravenous administration of 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin) over two to five minutes on days 1 and 8 of a three-week cycle. Since 2011, various clinical investigations of eribulin monotherapy with dose or schedule modifications, combined use with other antineoplastic therapeutics, or head-to-head comparisons with specific agents have been performed in the management of advanced breast cancer. Ethnic-specific data from Japan and Korea indicate higher rates (>85%) of grade 3 or 4 neutropenia. Some anecdotal evidence suggests that eribulin can shrink brain and retinal metastases, which warrants further detailed studies. In this review, current observations of the effects of eribulin monotherapy are summarized and eribulin-backbone combination (bio-) chemotherapy is investigated.


KEYWORDS: eribulin, metastatic breast cancer, triple-negative breast cancer, chemotherapy, medical oncology


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CITATION: Kok. Eribulin in the Management of Advanced Breast Cancer: Implications of Current Research Findings. Breast Cancer: Basic and Clinical Research 2015:9 109–115 doi:10.4137/BCBCR.S32787.

TYPE: Review

RECEIVED: October 20, 2015. RESUBMITTED: November 22, 2015. ACCEPTED FOR PUBLICATION: November 24, 2015.

ACADEMIC EDITOR: Goberdhan P. Dimri, Editor in Chief

PEER REVIEW: Four peer reviewers contributed to the peer review report. Reviewers’ reports totaled 1246 words, excluding any confidential comments to the academic editor.

FUNDING: Author discloses no external funding sources.

COMPETING INTERESTS: Author discloses no potential conflicts of interest. COPYRIGHT: © the authors, publisher and licensee Libertas Academica Limited. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.

CORRESPONDENCE: victorkok@asia.edu.tw Paper subject to independent expert blind peer review. All editorial decisions made by independent academic editor. Upon submission manuscript was subject to anti-plagiarism scanning. Prior to publication all authors have given signed confirmation of agreement to article publication and compliance with all applicable ethical and legal requirements, including the accuracy of author and contributor information, disclosure of competing interests and funding sources, compliance with ethical requirements relating to human and animal study participants, and compliance with any copyright requirements of third parties. This journal is a member of the Committee on Publication Ethics (COPE). Provenance: the author was invited to submit this paper.

Published by Libertas Academica. 


Introduction

Extensive research has been performed to isolate candidate new-generation antineoplastic cytotoxic drugs from marine natural products, including sponges and sea squirts.1,2 Among numerous sponge-derived cytotoxic compounds, only cytarabine and eribulin have received approval for clinical use. Although the former drug has been extensively used for the treatment of hematologic malignancies for decades, eribulin only gained approval in Japan in May 2010;3 it was approved by the US Food and Drug Administration (FDA) in November 20104 and the European Medicines Agency (EMA) in March 2011.5 The drug has only been reimbursed by the Taiwan National Health Insurance since December 2014 for patients with locally advanced or metastatic breast cancer who had received at least an anthracycline and a taxane.

Eribulin is a completely synthetic macrocyclic ketone analog of halichondrin B, which was initially isolated from the Japanese sponge Halichondria okadai in 1986 by Uemura and Hirata.6 In 1991, Pettit et al subsequently reported the isola­tion of halichondrin B from the Western Pacific marine sponge Axinella sp.7 Eribulin binds to tubulin and microtubules, inducing mitotic arrest and cell death. Moreover, eribulin exhibited growth inhibitory effects on stem cells (CD44/CD24/epithelial cell adhesion molecule) of both estrogen receptor (ER)-positive and ER-negative cell lines,8 warranting further research into these anticancer stem cell properties.

During the past four years, the therapeutic effects and adversities of eribulin monotherapy and eribulin-based combination therapies have been investigated in numerous studies. Hitherto, the purpose of this review is to assimilate all the relevant information from this literature to form the background knowledge for the incorporation of this agent into the current anti-breast cancer armamentarium.