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Low-dose eribulin reduces lung metastasis of osteosarcoma in vitro and in vivo.

ABSTRACT: Lung metastasis markedly reduces the prognosis of osteosarcoma. Moreover, there is no effective treatment for lung metastasis, and a new treatment strategy for the treatment of osteosarcoma lung metastasis is required. Therefore, in this study, we investigated the suppressive effect of the microtubule inhibitor eribulin mesylate (eribulin) on lung metastasis of osteosarcoma. At concentrations >proliferation IC50, eribulin induced cell cycle arrest and apoptosis in a metastatic osteosarcoma cell line, LM8. However, at concentrations

SUBMITTER: Watanabe K

PROVIDER: S-EPMC6349434 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Low-dose eribulin reduces lung metastasis of osteosarcoma in vitro and in vivo.

Watanabe Kenta K Yui Yoshihiro Y Sasagawa Satoru S Suzuki Kayo K Kanamori Masahiko M Yasuda Taketoshi T Kimura Tomoatsu T

Oncotarget 20190104 2

Lung metastasis markedly reduces the prognosis of osteosarcoma. Moreover, there is no effective treatment for lung metastasis, and a new treatment strategy for the treatment of osteosarcoma lung metastasis is required. Therefore, in this study, we investigated the suppressive effect of the microtubule inhibitor eribulin mesylate (eribulin) on lung metastasis of osteosarcoma. At concentrations >proliferation IC50, eribulin induced cell cycle arrest and apoptosis in a metastatic osteosa ...[more]

PMID: 30719211

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Project description:BackgroundTreatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician's choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile.MethodsWe conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy.FindingsWe consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients.InterpretationMetronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

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Low-dose eribulin reduces lung metastasis of osteosarcoma in vitro and in vivo.

Publications

Low-dose eribulin reduces lung metastasis of osteosarcoma <i>in vitro</i> and <i>in vivo</i>.

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