P17.64 * ANGIOGENIC AND PROCOAGULANT FACTORS IN PLASMA OF BRAIN TUMOUR PATIENTS TREATED WITH BEVACIZUMAB

Abstract

BACKGROUND: Glioblastoma (GBM) is one of the most vascularized human tumors and GBM cells produce proangiogenic factors, including vascular endothelial growth factor (VEGF). Bevacizumab (BV), a monoclonal antibody against VEGF, has shown antitumor activity, but so far no biomarkers have been identified to predict outcome. The purpose of the present study was to investigate the possible predictive value of circulating VEGF, von Willebrand factor (vWF) and procoagulant factors in patients with recurrent GBM. METHODS: We conducted a prospective analysis of recurrent malignant gliomas (MG) patients treated with BV alone or in combination with chemotherapy performing serial evaluations of plasma VEGF levels, vWF antigen and procoagulant factors such as thrombin-antithrombin complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), Factor VIII and D-Dimer. Baseline, and post-treatment samples were collected at each administration of BV. RESULTS: Forty-nine recurrent MGs (glioblastoma = 26, astrocytoma = 17, oligodendroglioma = 6) who received BV at 10 mg/kg intravenously every 3 weeks, of whom 26 in association with chemotherapy were included in the study. Median age was 45 years (22-73), median Karnofsky performance status was 80 (60-100). Out of the 48 evaluable, 17 partial responses (35%), 7 stable disease (15%) and 24 disease progressions (50%) were observed. At baseline all patients presented with laboratory signs of coagulation activation (i.e. high TAT and FVIII levels). Circulating plasma levels of VEGF and vWF antigen significantly increased in all patients post-treatment of BV (p = 0.0001 and 0.009 respectively). No responder patients showed significantly higher vWF antigen levels than responders (p = 0.01) after second administration of BV. CONCLUSIONS: These preliminary data suggest that low vWF antigen levels might help predict response in recurrent MG patients treated with BV. This marker should help clinicians to decide the right therapy, advise them of the generation of mechanisms of drug resistance during antiangiogenic treatment.