Vascular endothelial growth factor and von Willebrand factor levels: Clinical outcome in stage IV colorectal cancer

Abstract

3754 Background: von Willebrand factor (vWf) is thought to mediate binding of tumor cells to platelets, favouring their spreading capacity. Platelets involved in tumor angiogenesis are capable of releasing vascular endothelial growth factor (VEGF). Levels of vWf and VEGF may correlate with cancer stage and predict clinical outcome. The aim of this study was to correlate vWf and VEGF levels in stage IV colorectal cancer (CRC) patients undergoing chemotherapy (CMT) with response to treatment and time to progression (TTP). Methods: 25 metastatic CRC patients attending the Department of Oncology of our institution were enrolled in the study. Blood samples were taken before and after fluoropirimidine-based CMT, and stored until further processing. vWf, VEGF, platelet count, carcinoembrionary antigen (CEA) and CA 19.9 were measured using standardised techniques. Tumor burden assessed by number of locations of disease was also considered. Patients received a median of 3 cycles of CMT (range: 2–10) between both blood samples. Results: After 3 cycles of CMT, 11 patients showed stable disease (SD), 8 had responded partially (PR) and 6 patients showed progression (P). After a median follow-up of 9 months, 18 of 25 patients showed P, and the median TTP was 8.6 months. The hazard ratio (HR) (and its 95% confidence interval [CI]) for progression associated to an increase in one standard deviation in baseline levels of VEGF was 6.68 (2.45 – 18.18; p<0.001). For change in one standard deviation in the difference between VEGF levels after CMT and VEGF baseline levels, the HR for progression (95% CI) was 3.37 (1.34 – 8.49; p=0.01). In addition, considering vWf levels after CMT and vWf baseline levels, the HR for progression (95% CI) was 2.95 (1.37 – 6.34; p=0.006). These results were adjusted for age, gender, ECOG performance status and baseline platelet count. Adjusted additionally for CEA, CA 19.9 and tumor burden, no significant changes were found. Conclusions: VEGF serum pre-CMT levels and the increase of VEGF serum and vWf plasma levels during CMT may predict response to treatment and TTP in stage IV CRC patients. Supported by a grant of Gobierno de Navarra (RN 19/2003). No significant financial relationships to disclose.