PURPOSE: Noninvasive markers of anti-vascular endothelial growth factor (VEGF) therapy are needed. Soluble vascular cell adhesion molecule (sVCAM-1), soluble VEGF receptor-2 (sVEGFR-2), and plasma VEGF levels were assessed as potential biomarkers of therapy with bevacizumab. Tumor samples were evaluated for VEGFR-2 mutations before and after bevacizumab. EXPERIMENTAL DESIGN: Twenty-one patients with breast cancer underwent neoadjuvant treatment with bevacizumab for 1 cycle followed by 6 cycles of bevacizumab, chemotherapy, and filgrastim. Peripheral blood samples were collected at baseline, post cycles 1, 4 and 7. sVCAM-1, VEGF and sVEGFR-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). Exons 17-26 of VEGFR-2 were sequenced on tissue samples from 20 patients at baseline and post cycle 1 to evaluate for tumor mutations. RESULTS: From baseline to post cycle 1, sVCAM-1 and sVEGFR-2 values increased by a median of 180.5 ng/ml (p < 0.0001) and 1927 ng/ml respectively (p = 0.0003). Baseline VEGF, sVEGFR-2, and sVCAM-1 levels nor changes in sVEGFR-2 and sVCAM-1 levels were associated with clinical response. Median baseline sVEGFR-2 levels were 11322 ng/ml and 7524 ng/ml in patients with (n = 5) and without (n = 6) wound healing problems respectively, (p = 0.052). In 40 samples where tumor VEGFR-2 sequencing was obtained, no mutations were seen compared to the reference sequence. CONCLUSIONS: sVCAM-1 and sVEGFR-2 values increased significantly after treatment with bevacizumab, possibly due to compensatory mechanisms secondary to VEGF inhibition. sVEGFR-2 levels were somewhat higher in patients with wound healing problems and may potentially predict patients at higher risk of this complication. There were no tumor VEGFR-2 mutations.
PURPOSE: Noninvasive markers of anti-vascular endothelial growth factor (VEGF) therapy are needed. Soluble vascular cell adhesion molecule (sVCAM-1), soluble VEGF receptor-2 (sVEGFR-2), and plasma VEGF levels were assessed as potential biomarkers of therapy with bevacizumab. Tumor samples were evaluated for VEGFR-2 mutations before and after bevacizumab. EXPERIMENTAL DESIGN: Twenty-one patients with breast cancer underwent neoadjuvant treatment with bevacizumab for 1 cycle followed by 6 cycles of bevacizumab, chemotherapy, and filgrastim. Peripheral blood samples were collected at baseline, post cycles 1, 4 and 7. sVCAM-1, VEGF and sVEGFR-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). Exons 17-26 of VEGFR-2 were sequenced on tissue samples from 20 patients at baseline and post cycle 1 to evaluate for tumor mutations. RESULTS: From baseline to post cycle 1, sVCAM-1 and sVEGFR-2 values increased by a median of 180.5 ng/ml (p < 0.0001) and 1927 ng/ml respectively (p = 0.0003). Baseline VEGF, sVEGFR-2, and sVCAM-1 levels nor changes in sVEGFR-2 and sVCAM-1 levels were associated with clinical response. Median baseline sVEGFR-2 levels were 11322 ng/ml and 7524 ng/ml in patients with (n = 5) and without (n = 6) wound healing problems respectively, (p = 0.052). In 40 samples where tumorVEGFR-2 sequencing was obtained, no mutations were seen compared to the reference sequence. CONCLUSIONS: sVCAM-1 and sVEGFR-2 values increased significantly after treatment with bevacizumab, possibly due to compensatory mechanisms secondary to VEGF inhibition. sVEGFR-2 levels were somewhat higher in patients with wound healing problems and may potentially predict patients at higher risk of this complication. There were no tumorVEGFR-2 mutations.
Authors: Tanya B Dorff; Bryan Goldman; Jacek K Pinski; Philip C Mack; Primo N Lara; Peter J Van Veldhuizen; David I Quinn; Nicholas J Vogelzang; Ian M Thompson; Maha H A Hussain Journal: Clin Cancer Res Date: 2010-05-18 Impact factor: 12.531
Authors: Efstathios T Pavlidis; Konstantinos D Ballas; Nikolaos G Symeonidis; Kyriakos Psarras; Georgios Koliakos; Kokona Kouzi-Koliakos; Konstantina Topouridou; Savas F Rafailidis; Theodoros E Pavlidis; Georgios N Marakis; Athanasios K Sakantamis Journal: Int J Colorectal Dis Date: 2010-08-06 Impact factor: 2.571
Authors: Brian Rini; Cezary Szczylik; Nizar M Tannir; Piotr Koralewski; Piotr Tomczak; Andrzej Deptala; Luc Y Dirix; Mayer Fishman; Rodryg Ramlau; Alain Ravaud; Wojciech Rogowski; Karolyn Kracht; Yu-Nien Sun; Michael B Bass; Markus Puhlmann; Bernard Escudier Journal: Cancer Date: 2012-06-12 Impact factor: 6.860
Authors: Scott Kopetz; Paulo M Hoff; Jeffrey S Morris; Robert A Wolff; Cathy Eng; Katrina Y Glover; Rosie Adinin; Michael J Overman; Vincete Valero; Sijin Wen; Christopher Lieu; Shaoyu Yan; Hai T Tran; Lee M Ellis; James L Abbruzzese; John V Heymach Journal: J Clin Oncol Date: 2009-12-14 Impact factor: 44.544