Is metronomic vinorelbine (mVRL) able to inhibit both HUVEC and triple-negative breast cancer (TNBC) cells? The proof-of-concept VICTOR-0 study.

• DOI: 10.1200/jco.2017.35.15_suppl.e14014
• Publication Date: 2018-09-06T16:03:02Z
• Authors: Maria Grazia Cerrito; Davide Pelizzoni; Marco De Giorgi; Nunzio Digiacomo; Marialuisa Lavitrano; Roberto Giovannoni; Paolo Bidoli; Marina Elena Cazz...
• Keywords: Vinorelbine; Triple-negative breast cancer

e14014 Background: TNBC represents an important clinical challenge because of poor prognosis. One the emerging strategy to achieve disease control while reducing toxicity is metronomic chemotherapy (mCHT) which targets endothelial cells (ECs) and inhibits tumor growth. mVRL a promising option in patients (pts) with metastatic breast cancer (MBC), resulting median PFS 7.7 months OS 15.9. To better explain effect we studied effects doses VRL vitro models compared them standard same drug. Methods: Cell viability cytotoxicity assays were performed on (MDA-MB-231) Human Umbilical Vein Endothelial Cells (HUVEC). lines exposed different concentration (0,01nM-1mM) for 4 96 h. simulate dosing schedule, replaced drug-enriched medium every 24h, conventional administration protocol (sCHT) 4h, then was changed fresh without drug 24 The IC 50 calculated by non-linear regression fit mean values data obtained triplicate experiments. Results: A significant anti-proliferative activity observed both HUVEC MDA treated mCHT as sCHT (see Table). These lower concentrations did not have remarkable cell death. Conversely, higher dose utilized produced death well HUVEC, even if vivo, inducing largest apoptosis also affectd healthy proliferating causing toxicity. Our findings suggest that inhibited proliferation tumour can block progression minor side effects. Conclusions: This study provides proof-of-concept VRL, but ones, are able inhibit, at concentration, ECs cells. trial TEMPO-BREAST, compares vs ongoing MBC pts. [Table: see text]