PMC:4822111 / 1113-4714 JSONTXT

{"project":"2_test","denotations":[{"id":"27066091-14692023-56335760","span":{"begin":322,"end":323},"obj":"14692023"},{"id":"27066091-23020297-56335761","span":{"begin":322,"end":324},"obj":"23020297"},{"id":"27066091-17647245-56335762","span":{"begin":322,"end":325},"obj":"17647245"},{"id":"27066091-20555067-56335763","span":{"begin":516,"end":517},"obj":"20555067"},{"id":"27066091-18224392-56335764","span":{"begin":810,"end":811},"obj":"18224392"},{"id":"27066091-11221827-56335765","span":{"begin":1216,"end":1217},"obj":"11221827"},{"id":"27066091-16020666-56335766","span":{"begin":1535,"end":1536},"obj":"16020666"},{"id":"27066091-16020666-56335767","span":{"begin":1652,"end":1653},"obj":"16020666"},{"id":"27066091-18645010-56335768","span":{"begin":1652,"end":1654},"obj":"18645010"},{"id":"27066091-21127197-56335769","span":{"begin":1765,"end":1766},"obj":"21127197"},{"id":"27066091-19509177-56335770","span":{"begin":2177,"end":2179},"obj":"19509177"},{"id":"27066091-19509146-56335771","span":{"begin":2177,"end":2181},"obj":"19509146"}],"text":"INTRODUCTION\nImproving overall survival (OS) remains an important treatment goal in metastatic breast cancer (mBC) patients. Despite the introduction of several novel therapies in recent years, mBC remains incurable; therefore, research continues to focus on developing treatments that could potentially improve survival [123].\nTreatment approaches in the second- and later-line disease settings vary according to multiple factors, and no chemotherapeutic agent has clearly demonstrated superiority over the others [4]. In view of the palliative aim of mBC treatment, there is a trade-off between the benefits of chemotherapy and its associated toxic side effects. In everyday clinical practice, treatment choice is, therefore, determined based on the individual patient's condition and tumor characteristics [5]. With this in mind, physicians need to be familiar with the available therapies, in addition to the management of side effects associated with such therapies.\nEribulin is a synthetic analog of halichondrin B, which is a naturally occurring molecule with antitumor properties that was originally isolated from a marine sponge (Halichondria okadai) found in the Pacific Ocean close to the coast of Japan [6]. Eribulin is a microtubule-targeted chemotherapeutic agent that belongs to the halichondrin class of molecules. It inhibits mitotic spindle formation by selectively targeting the microtubule growth phase, without affecting the shortening phase, which results in decreased cell proliferation and increased apoptosis [7]. This mode of action is distinct from those of other tubulin-targeting agents such as vinblastine and paclitaxel [78]. Eribulin induces an irreversible mitotic blockade, an action that is uncommon among microtubule inhibitors [9]. In addition to its antimitotic effects, eribulin may cause tumor vasculature remodeling and the reversal of epithelial-mesenchymal transition, which may decrease the invasiveness and metastasis of tumor cells [101112].\nThe pharmacokinetic profile of eribulin is characterized by a rapid distribution phase, followed by a prolonged elimination phase; its average terminal half-life is approximately 40 hours [1314]. Eribulin is weakly bound to plasma proteins; at a concentration between 100 and 1,000 ng/mL, the plasma protein binding in human plasma ranged from 49% to 65% [15]. Eribulin has a low clearance rate (range of means, 1.16–2.42 L/h/m2), with no significant accumulation upon weekly administration. When the dose of eribulin falls between 0.22 and 3.53 mg/m2, the pharmacokinetic properties are not dose- or time-dependent [15]. Eribulin is mainly eliminated through biliary excretion. Based on a pharmacokinetic study, approximately 82% of the eribulin administered was eliminated in the feces, and 9% in the urine, which indicate that renal clearance is not a significant elimination route in the case of eribulin [15].\nThe approval of eribulin for the treatment of patients with locally advanced breast cancer (LABC) or mBC pretreated with an anthracycline and a taxane was based on the results of its phase II and III clinical trial that enrolled patients mainly from Western countries. In many Asian countries, eribulin has only recently been approved, and Asian clinicians in certain countries have limited experience of using it in their clinical practice. In this paper, we summarize the key clinical information associated with eribulin for the treatment of mBC, and provide practical guidance for its use, including the management of its adverse events (AEs) based on our clinical experience in Asian patients."}