Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas

Abstract

Although the overall survival of advanced soft-tissue sarcoma (STS) patients has increased in recent years, the median progression-free survival is lower than 5 months, meaning that there is an unmet need in this population. Among second-line treatments for advanced STS, eribulin is an anti-microtubule agent that has been approved for liposarcoma. Here, we tested the combination of eribulin with gemcitabine in preclinical models of L-sarcoma. The effect in cell viability was measured by MTS and clonogenic assay. Cell cycle profiling was studied by flow cytometry, while apoptosis was measured by flow cytometry and Western blotting. The activity of eribulin plus gemcitabine was evaluated in in vivo patient-derived xenograft (PDX) models. In L-sarcoma cell lines, eribulin plus gemcitabine showed to be synergistic, increasing the number of hypodiploid events (increased subG1 population) and the accumulation of DNA damage. In in vivo PDX models of L-sarcomas, eribulin combined with gemcitabine was a viable scheme, delaying tumour growth after one cycle of treatment, being more effective in leiomyosarcoma. The combination of eribulin and gemcitabine was synergistic in L-sarcoma cultures and it showed to be active in in vivo studies. This combination deserves further exploration in the clinical context.

Eribulin and irinotecan (ERII) for refractory or recurrent Ewing sarcoma: a retrospective study

“…It was approved in the United States in 2010 for the second-line treatment of metastatic breast cancer and in 2016 for liposarcoma. The cell cycle-dependent MOA and good safety record make eribulin an ideal partner for systemic therapies, such as anti-angiogenesis TKI (levantinib 20 ) or gemcitabine 21 for liposarcoma and leiomyosarcoma or immune checkpoint inhibitors for urothelial carcinoma 22 and breast cancer 23 . Eribulin has usually been given at a dose of 1.4 mg/m 2 IV on days 1 and 8 of a 21-day cycle, the recommended dose for monotherapy.…”

Chemotherapeutic drugs for soft tissue sarcomas: a review

“…The efficacy of gemcitabine in combination with other drugs for STSs is inferior to that of docetaxel plus gemcitabine ( Table 5 ). In addition, gemcitabine in combination with emerging drugs, such as pazopanib and eribulin, has also been tested for the treatment of STSs ( Somaiah et al, 2021 ; Lopez-Alvarez et al, 2022 ). In summary, gemcitabine and docetaxel have similar efficacy and status in the treatment of STSs.…”

Sarcoma: Molecular Pathology, Diagnostics, and Therapeutics

“…Among the new anticancer drugs, eribulin, an anti-microtubule agent, has demonstrated antitumour effects in patients with L-sarcoma. In this Special Issue, López-Álvarez et al demonstrated the efficacy of eribulin combined with gemcitabine in preclinical models of L-sarcoma [ 7 ]. In L-sarcoma cell lines, the combination of eribulin and gemcitabine was shown to have synergistic effects, increasing the number of hypodiploid events and the accumulation of DNA damage.…”