Abstract
Abstract Purpose: Eribulin mesylate (eribulin) is a first-in-class halichondrin B-based microtubule dynamics inhibitor. To understand the mechanism of vascular remodeling of eribulin, we compared optical hemodynamic and blood biomarker changes between eribulin and bevacizumab. Methods: Patients with advanced breast cancer with stage III/IV were eligible for the study. Patients were assigned to receive either eribulin or single-agent bevacizumab. Diffuse optical spectroscopic imaging (DOSI) measured tissue concentrations of oxy-hemoglobin (O2Hb), deoxy-hemoglobin (HHb), total hemoglobin (tHb) and oxygen saturation (SO2) of breast tumors before and day 7 after the first infusion. Peripheral blood samples were obtained from the patients to measure plasma concentration of VEGF, bFGF, FLT-3L, EGF, G-CSF, TNFα, IL1b, IL4, IL6, IL8, IL10, IL12p40, and TGF-β1. Results: Baseline DOSI measurement of all 29 patients (eribulin, n = 14 and bevacizumab, n = 15) revealed significantly higher tumor concentrations of O2Hb, HHb, and tHb than that in the normal breast tissue. Eribulin significantly decreased in HHb concentration and increased SO2 during the observation period. This trend was not observed for bevacizumab. Instead, bevacizumab significantly decreased the concentration of O2Hb and tHb. The blood biomarker study revealed that both eribulin and bevacizumab decreased plasma concentrations of VEGF and bFGF, but only eribulin suppressed the plasma concentration of TGF-β1. Conclusions: Optical imaging technology revealed that eribulin, but not bevacizumab, induced tumor reoxygenation after the start of infusion. Eribulin had a potent anti-angiogenic properties as well as bevacizumab, while suppression of TGF-β1 observed by only eribulin could be associated with remodeling of the microvasculature through suppression of activated stromal cells. Citation Format: Ueda S, Saeki TS, Takeuchi H, Shigekawa T, Yamane T, Kuji I, Osaki A. Eribulin induces vascular remodeling and reoxygenation in advanced breast cancer patients: A comparative study with bevacizumab [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-02-01.
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