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OBJECTIVE: Eribulin mesylate (Halaven®) is a non-taxane inhibitor of microtubule indicated as monotherapy in patients with metastatic breast cancer (MBC), which progresses after anthracycline and taxanes therapy. In this retrospective observational study, we want to evaluate the efficacy of Eribulin in elderly women with MBC pretreated with anthracyclines and taxanes. PATIENTS AND METHODS: 40 elderly patients > 70 years of age were enrolled, and the median age was 76 years (range 70-82). Overall survival (OS), Progression Free Survival (PFS), Objective Response Rate (ORR) were primary endpoints, tolerability, carcinoembryonic antigen levels 15.3 (Ca 15.3), before and after treatment, and Quality of Life (QoL) were secondary endpoints. RESULTS: Eribulin treatment was well tolerated, produced a good level of disease control, a manageable toxicity profile and a significant impact on QoL. Median OS was 12.8 months and median PFS was 3.2 months. A significant correlation was observed between reduction of Ca 15.3 and PFS with a value of 0.59 (p = 0.002). CONCLUSIONS: Despite a limited number of patients and a modest manageable toxicity, Eribulin is a chemotherapy treatment that has showed to be an effective and well-tolerated therapeutic option in elderly patients with MBC. Further analysis should focus on the elderly patients in our setting of study. [ABSTRACT FROM AUTHOR]

The article deals with the results of the administration of new cytostatic - eribulin (Halaven). In EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) phase III clinical study, Halaven had been administrated to 6 patients (between 6 and 35 cycles), at that, partial tumor regression was observed in 3 patients and other 3 patients achieved stabilization. Median progression-free survival (PFS) was 15,3 months and median duration of response (DOR) was 13 months in eribulin group, in group of treatment of physician's choice - median PFS was 5,3 and median DOR was 3,3 months. This article demonstrates 3 clinical cases. The authors concluded that eribulin showed high effectiveness and meaningful improvement in overall survival, maintaining the high quality of life.

Data from two phase 3 studies of eribulin were pooled in analyses initially requested by the European Medicines Agency to assess whether specific patient subgroups, previously treated with an anthracycline and a taxane, benefited from eribulin. Study 305/EMBRACE included women after two-to-five lines of chemotherapy for advanced breast cancer who were randomized to eribulin mesylate (1.4 mg/m on days 1 and 8 every 21 days) or treatment of physician's choice. In Study 301, patients who had received up to two prior chemotherapy regimens for advanced disease were randomized to eribulin (as above) or capecitabine (1.25 g/m b.i.d. on days 1-14 every 21 days). In the pooled population, overall survival (OS), progression-free survival and response rates were analysed in the intent-to-treat population and selected subgroups. Overall, 1,062 patients were randomized to eribulin and 802 patients to control. Median OS was 15.2 months with eribulin versus 12.8 months with control (hazard ratio [HR] 0.85; 95 % CI 0.77, 0.95; P = 0.003). In all subgroups assessed, OS data favoured eribulin; significant improvements occurred in some subgroups, notably in women with human epidermal growth factor receptor 2 (HER2)-negative disease (HR 0.82; P = 0.002), although the effect in those with HER2-negative but hormone-receptor-positive disease did not reach statistical significance; benefits were also seen, among others, in those with estrogen-receptor-negative and triple-negative disease. Eribulin improves OS in various patient subgroups with advanced/metastatic breast cancer who had previously received an anthracycline and a taxane. Women with HER2-negative disease are among those who may obtain benefit from eribulin. [ABSTRACT FROM AUTHOR]

Abstract: A series of eribulin analogues was evolved in silico through iterative atom-based enumeration employing a genetic algorithm-derived survival function to minimize predicted PgP-mediated drug efflux. Representatives of the virtual series were subsequently synthesized in the laboratory and tested in vitro for PgP-susceptibility. These new computer-inspired derivatives were found to exhibit high cell growth inhibitory activity and to be among the least sensitive to P-glycoprotein-mediated drug efflux in the eribulin series, thereby validating this approach to in silico molecular design. [Copyright &y& Elsevier]

Abstract: Background: Eribulin mesylate is a halichondrin B analogue that acts as a nontaxane microtubule dynamics inhibitor. Eribulin was approved in the United States in 2010 for the treatment of metastatic breast cancer for patients who have received at least 2 metastatic breast cancer chemotherapeutic regimens, including an anthracycline and a taxane. Eribulin is administered as a single agent at 1.4 mg/m2 IV for 2 to 5 minutes on days 1 and 8 of a 21-day cycle. Objectives: The goals of this article are to review eribulin''s medication profile, including pharmacology, pharmacokinetic properties, efficacy, and tolerability. Recommendations are provided at the end of the article based on the published information. Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Clinical Trials.gov were searched from the beginning of each database through January 3, 2012, for relevant articles on human studies published in English. Search terms included eribulin, eribulin mesylate, and Halaven. Clinical trials, case reports, comparative studies, meta-analyses, evaluation studies, controlled clinical trials, and randomized controlled trials were included as search limits. The references from selected articles were also reviewed to identify additional publications. Eisai, the manufacturer of eribulin mesylate, was also contacted for information regarding trials listed in Clinicaltrials.gov but not yet published. Results: One Phase III trial was identified that evaluated eribulin for use in patients with metastatic breast cancer. Four Phase II trials were identified that studied eribulin in patients with head and neck, pancreatic, and non–small cell lung cancers. The median overall survival among previously treated metastatic breast cancer patients treated with eribulin was 13.1 months compared with 10.6 months (P = 0.041) with other active chemotherapy for this setting. In non–small cell lung cancer, median overall survival in eribulin-treated patients has been reported as 9.4 months in an unselected population and varies according to taxane sensitivity: 12.6 months in taxane-sensitive disease versus 8.9 months in taxane-resistant disease. Patients with head and neck or pancreatic cancers did not experience improvements in response rates or survival outcomes when treated with eribulin in clinical trials. Conclusions: Eribulin is approved by the Food and Drug Administration for patients with previously treated metastatic breast cancer and has demonstrated a survival benefit compared with standard treatment options in this setting. Non–small cell lung cancer patients had improved response rates when treated with eribulin in open-label, nonrandomized, Phase II trials reported in abstract form. Eribulin was not effective in the treatment of head and neck or pancreatic cancer in Phase II trials. [Copyright &y& Elsevier]

Background/aim: Eribulin mesylate, also called Halaven® (HAL), was recently developed as a microtubule-targeting drug and is used in the clinic for resistant or metastatic cancer. Previously, we showed that P-glycoprotein (P-gp)-overexpressing KBV20C oral cancer cells are highly resistant to HAL compared to sensitive KB cells. This qualitative study was designed to identify specific P-gp inhibitors that increase the sensitivity of highly resistant cancer cells to HAL., Materials and Methods: In order to identify functional P-gp inhibitors, HAL-treated KBV20C cells were co-treated with P-gp inhibitors, verapamil, elacridar, cyclosporine A, mitotane, piperine, fumagillin, curcumin, indomethacin, probenecid, sulindac, tesmilifene, and C-4. We then evaluated which P-gp inhibitors required a low dose to sensitize KBV20C cells to HAL. We also determined whether a low dose of a P-gp inhibitor could inhibit P-gp efflux pumping., Results: We found that cyclosporine A sensitized HAL-treated KBV20C cells at a low dose, whereas verapamil, another first-generation P-gp inhibitor, required a dose that was nearly 10-fold higher. We also found that the natural products, piperine and mitotane, sensitized KBV20C cells to HAL co-treatment. Interestingly, we found that elacridar, a third-generation P-gp inhibitor, sensitized HAL-treated cells at a low dose. Elacridar required approximately a 500-fold lower dose than that of verapamil to exert a similar effect. All inhibitors showed P-gp inhibitory activity that correlated with sensitivity to HAL., Conclusion: These results suggest that highly HAL-resistant cancer cells can be sensitized with cyclosporine A or elacridar, specific P-gp inhibitors that exert their effects at a low dose. These findings provide important information regarding the sensitization of highly HAL-resistant cells with selective P-gp inhibitors and indicate that elacridar may be used to treat such highly HAL-resistant cancer cells., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Eribulin is a non-taxane, macrocyclic, synthetic, ketone analog of halichondrin B with a microtubule inhibitory action specific toward plus ends. It is approved by United States Food and Drug Administration (USFDA) for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen. It is also approved as a third line therapy for patients with metastatic breast cancer who have received a prior treatment with anthracycline and taxane in either adjuvant or metastatic setting. It has also undergone investigation in various cancers including non-small cell lung cancer (NSCLC). Areas covered: This review covers eribulin in detail with regards to pharmacodynamics, mechanism of action, pharmacokinetics, published phase I studies along with special focus on phase II and III studies of eribulin in NSCLC. Expert opinion: Eribulin is a potent chemotherapeutic agent with acceptable and easily manageable toxicity profile. It has shown activity in NSCLC. However, the management of NSCLC is undergoing rapid evolution with introduction of newer immune mediated and targeted agents. The way to move forward is to combine eribulin with novel immune checkpoint inhibitors, targeted agents and chemotherapies in appropriate line of therapy.

Aim: To identify conditions that induce an increase in the sensitivity of highly Halaven (HAL)-resistant cancer cells compared to sensitive cells., Materials and Methods: We observed that drug-resistant KBV20C cells are highly resistant to HAL compared to other antimitotic drugs. The concentration required to treat KBV20C cells was almost 500-fold higher than that used to treat sensitive parent KB cells. In order to increase sensitization, HAL-treated KBV20C cells were co-treated with the repositioned drug, fluphenazine (FLU)., Results: HAL and FLU co-treatment inhibited the growth and increased apoptosis via G 2 arrest in HAL-treated KBV20C cancer cells. Sensitization by HAL-FLU affected retinoblastoma protein (pRB), pHistone H3 and pH2AX protein levels. FLU could also inhibit p-glycoprotein (P-gp) activity in HA-resistant KBV20C cells. These observations suggest that the mechanisms underlying FLU-HAL sensitization in resistant KBV20C cells involve both apoptosis and P-gp inhibition. Furthermore, both thioridazine (THIO) and mefloquine (MEF), but not azathioprine (AZA), sensitized HAL-treated KBV20C cells., Conclusion: These findings provide important information regarding the sensitization of HAL-resistant cells and indicate that FLU, THIO and MEF may have similar sensitization effects in highly HAL-resistant cells., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The present phase II, open-label, multicenter study explored the feasibility, safety, and tolerability of eribulin, a novel non-taxane microtubule inhibitor, plus capecitabine as adjuvant therapy., Patients and Methods: Postmenopausal women with early-stage, human epidermal growth factor receptor 2 (HER2)-negative, estrogen-receptor (ER)-positive breast cancer received four 21-day cycles of treatment with eribulin mesylate (1.4 mg/m(2) intravenously on days 1 and 8 of each cycle) combined with capecitabine (900 mg/m(2) orally twice daily on days 1-14 of each cycle [standard schedule] or 1500 mg orally twice daily using a 7-days on/7-days off schedule [weekly schedule]). Feasibility was determined by the relative dose intensity (RDI) of the combination using prespecified criteria for 80% of patients achieving an RDI of ≥ 85%, with a lower 95% confidence boundary > 70%., Results: The mean RDI was 90.6%, and the feasibility rate was 81.3% among women (n = 67, mean age, 61.3 years) receiving the standard schedule and 95.6% and 100% among women (n = 10, mean age 62.3 years) receiving the weekly schedule. Dose reductions, missed doses, and withdrawals due to adverse events (most commonly hand-foot syndrome) ascribed to capecitabine led to a higher RDI (93.5% vs. 87.8%) and feasibility rate (82.8% vs. 71.9%) for eribulin than for capecitabine using the standard dosing schedule. The most common adverse events were alopecia and fatigue., Conclusion: Eribulin plus capecitabine with standard or weekly dosing schedules is feasible in patients with early-stage, HER2-negative, ER-positive breast cancer. Full-dose eribulin (1.4 mg/m(2) on days 1 and 8) with capecitabine (1500 mg orally twice daily, 7 days on/7 days off) is recommended as a regimen for further evaluation., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)