Eribulin in Cancer Treatment

Swami, Umang; Shah, Umang; Goel, Sanjay

doi:10.3390/md13085016

Cited by 62 publications

(36 citation statements)

References 95 publications

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“… 111 – 113 In this regard, eribulin has been found to be especially efficacious in patients with tumours harbouring beta-tubulin mutations that are refractory to taxanes. 114 , 115 In preclinical models, eribulin was shown to induce an irreversible mitotic arrest, apoptosis and tumour regression in multiple cancer cell lines with a mean IC50 that is 2–4-fold more potent than vinblastine and paclitaxel. 114 , 116 , 117 A broad range of sarcoma cell lines, including liposarcoma, leiomyosarcoma, Ewing’s sarcoma, synovial sarcoma and fibrosarcoma, have been demonstrated to be sensitive to eribulin.…”

Section: Systemic Control In Sarcomamentioning

confidence: 99%

Managing sarcoma: where have we come from and where are we going?

et al. 2017

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Sarcomas are a heterogeneous group of neoplasms of mesenchymal origin. Approximately 80% arise from soft tissue and 20% originate from bone. To date more than 100 sarcoma subtypes have been identified and they vary in molecular characteristics, pathology, clinical presentation and response to treatment. While sarcomas represent <1% of adult cancers, they account for approximately 21% of paediatric malignancies and thus pose some of the greatest risks of mortality and morbidity in children and young adults. Metastases occur in one-third of all patients and approximately 10–20% of sarcomas recur locally. Surgery in combination with preoperative and postoperative therapies is the primary treatment for localized sarcoma tumours and is the most promising curative possibility. Metastasized sarcomas, on the other hand, are treated primarily with single-agent or combination chemotherapy, but this rarely leads to a complete and robust response and often becomes a palliative form of treatment. The heterogeneity of sarcomas results in variable responses to current generalized treatment strategies. In light of this and the lack of curative strategies for metastatic and unresectable sarcomas, there is a need for novel subtype-specific treatment strategies. With the more recent understanding of the molecular mechanisms underlying the pathogenesis of some of these tumours, the treatment of sarcoma subtypes with targeted therapies is a rapidly evolving field. This review discusses the current management of sarcomas as well as promising new therapies that are currently underway in clinical trials.

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Section: Systemic Control In Sarcomamentioning

confidence: 99%

Managing sarcoma: where have we come from and where are we going?

et al. 2017

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“…Eribulin is currently approved in more than 60 countries for the treatment of refractory breast cancers and liposarcomas. In a series of preliminary preclinical experiments, eribulin showed anticancer activities in diverse cancer cell lines, including a GBM cell line . In this study, we investigated the efficacy of eribulin in inhibiting GBM cell proliferation in vitro and in vivo , as well as the pharmacokinetics of eribulin in a mouse harboring intracerebrally‐transplanted human GBM cells.…”

Section: Introductionmentioning

confidence: 99%

“…In a series of preliminary preclinical experiments, eribulin showed anticancer activities in diverse cancer cell lines, including a GBM cell line. [27][28][29] In this study, we investigated the efficacy of eribulin in inhibiting GBM cell proliferation in vitro and in vivo, as well as the pharmacokinetics of eribulin in a mouse harboring intracerebrally-transplanted human GBM cells. Our results showed that eribulin is active against GBM with TERT promoter mutations and penetrated mouse brain tumors.…”

Section: Introductionmentioning

confidence: 99%

Eribulin penetrates brain tumor tissue and prolongs survival of mice harboring intracerebral glioblastoma xenografts

Takahashi¹,

Miki²,

Fujimoto³

et al. 2019

Cancer Science

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Glioblastoma is one of the most devastating human malignancies for which a novel efficient treatment is urgently required. This pre–clinical study shows that eribulin, a specific inhibitor of telomerase reverse transcriptase (TERT)‐RNA‐dependent RNA polymerase, is an effective anticancer agent against glioblastoma. Eribulin inhibited the growth of 4 TERT promoter mutation‐harboring glioblastoma cell lines in vitro at subnanomolar concentrations. In addition, it suppressed the growth of glioblastoma cells transplanted subcutaneously or intracerebrally into mice, and significantly prolonged the survival of mice harboring brain tumors at a clinically equivalent dose. A pharmacokinetics study showed that eribulin quickly penetrated brain tumors and remained at a high concentration even when it was washed away from plasma, kidney or liver 24 hours after intravenous injection. Moreover, a matrix‐assisted laser desorption/ionization mass spectrometry imaging analysis revealed that intraperitoneally injected eribulin penetrated the brain tumor and was distributed evenly within the tumor mass at 1 hour after the injection whereas only very low levels of eribulin were detected in surrounding normal brain. Eribulin is an FDA‐approved drug for refractory breast cancer and can be safely repositioned for treatment of glioblastoma patients. Thus, our results suggest that eribulin may serve as a novel therapeutic option for glioblastoma. Based on these data, an investigator‐initiated registration‐directed clinical trial to evaluate the safety and efficacy of eribulin in patients with recurrent GBM (UMIN000030359) has been initiated.

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“…Eribulin was responsible for prolonging overall survival (OS) of heavily pretreated metastatic breast cancer patients in a large Phase III trial ( Cortes et al , 2011 ) and is now under clinical development in earlier settings such as neoadjuvant and adjuvant settings. Furthermore, its unique mechanism of action and the absence of cross-resistance with taxanes have led to the design of clinical trials in multiple indications including: bladder, lung and prostate cancers ( Polastro et al , 2014 ; Swami et al , 2015 ). On the basis of the promising results from the phase II ( Schöffski et al , 2011 ), a randomised, open-label, multicenter phase III trial of eribulin mesylate in patients with locally advanced or recurrent and/or metastatic adipocytic sarcoma or leiomyosarcoma was conducted (NCT01327885).…”

Section: Discussionmentioning

confidence: 99%

A phase I combination dose-escalation study of eribulin mesylate and gemcitabine in patients with advanced solid tumours: a study of the Princess Margaret Consortium

et al. 2015

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Background:Eribulin mesylate is a synthetic microtubule inhibitor that showed cytotoxic synergy in combination with gemcitabine preclinically. This combination was assessed in a Phase I dose-finding trial in patients diagnosed with advanced solid tumours who had received up to two prior chemotherapy regimens for metastatic disease (CP cohort).Methods:Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated.Results:45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0 mg m−2 eribulin and 1000 mg m−2 gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts – 2/21 (CP), 1/10 (G) and 2/14 (CN).Conclusions:The combination of eribulin and gemcitabine was well tolerated at the RP2D.

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Eribulin in Cancer Treatment

Cited by 62 publications

References 95 publications

Managing sarcoma: where have we come from and where are we going?

Managing sarcoma: where have we come from and where are we going?

Eribulin penetrates brain tumor tissue and prolongs survival of mice harboring intracerebral glioblastoma xenografts

A phase I combination dose-escalation study of eribulin mesylate and gemcitabine in patients with advanced solid tumours: a study of the Princess Margaret Consortium

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