Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins
BACKGROUND:Sunitinib malate (SUTENT(R)) is an oral, multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC and of imatinib-resistant or - intolerant GIST. The purpose of this study was to explore potential biomarkers of sunitinib pharmacological activity via serial assessment of plasma levels of four soluble proteins from patients in a phase II study of advanced RCC: VEGF, soluble VEGFR-2 (sVEGFR-2), placenta growth factor (PlGF), and a novel soluble variant of VEGFR-3 (sVEGFR-3).METHODS:Sunitinib was administered at 50 mg/day on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment) to 63 patients with metastatic RCC after failure of first-line cytokine therapy. Predose plasma samples were collected on days 1 and 28 of each cycle and analyzed via ELISA.RESULTS:At the end of cycle 1, VEGF and PlGF levels increased >3-fold (relative to baseline) in 24/54 (44%) and 22/55 (40%) cases, respectively (P < 0.001). sVEGFR-2 levels decreased g
%0 Journal Article
%1 Deprimo.2007b
%A Deprimo, Samuel
%A Bello, Carlo
%A Smeraglia, John
%A Baum, Charles
%A Spinella, Dominic
%A Rini, Brian
%A Michaelson, M. Dror
%A Motzer, Robert
%D 2007
%J Journal of Translational Medicine
%K Carcinoma Disease Placenta Progression Proteins Tyrosine analysis protein response therapy
%N 1
%P 32
%T Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins
%U http://www.translational-medicine.com/content/5/1/32
%V 5
%X BACKGROUND:Sunitinib malate (SUTENT(R)) is an oral, multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC and of imatinib-resistant or - intolerant GIST. The purpose of this study was to explore potential biomarkers of sunitinib pharmacological activity via serial assessment of plasma levels of four soluble proteins from patients in a phase II study of advanced RCC: VEGF, soluble VEGFR-2 (sVEGFR-2), placenta growth factor (PlGF), and a novel soluble variant of VEGFR-3 (sVEGFR-3).METHODS:Sunitinib was administered at 50 mg/day on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment) to 63 patients with metastatic RCC after failure of first-line cytokine therapy. Predose plasma samples were collected on days 1 and 28 of each cycle and analyzed via ELISA.RESULTS:At the end of cycle 1, VEGF and PlGF levels increased >3-fold (relative to baseline) in 24/54 (44%) and 22/55 (40%) cases, respectively (P < 0.001). sVEGFR-2 levels decreased g
@article{Deprimo.2007b,
abstract = {BACKGROUND:Sunitinib malate (SUTENT(R)) is an oral, multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC and of imatinib-resistant or - intolerant GIST. The purpose of this study was to explore potential biomarkers of sunitinib pharmacological activity via serial assessment of plasma levels of four soluble proteins from patients in a phase II study of advanced RCC: VEGF, soluble VEGFR-2 (sVEGFR-2), placenta growth factor (PlGF), and a novel soluble variant of VEGFR-3 (sVEGFR-3).METHODS:Sunitinib was administered at 50 mg/day on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment) to 63 patients with metastatic RCC after failure of first-line cytokine therapy. Predose plasma samples were collected on days 1 and 28 of each cycle and analyzed via ELISA.RESULTS:At the end of cycle 1, VEGF and PlGF levels increased >3-fold (relative to baseline) in 24/54 (44%) and 22/55 (40%) cases, respectively (P < 0.001). sVEGFR-2 levels decreased [g},
added-at = {2010-02-05T11:28:39.000+0100},
author = {Deprimo, Samuel and Bello, Carlo and Smeraglia, John and Baum, Charles and Spinella, Dominic and Rini, Brian and Michaelson, M. Dror and Motzer, Robert},
biburl = {https://www.bibsonomy.org/bibtex/2981e8be5006d7a7a3b0abdb91c21ae8f/kanefendt},
interhash = {fb9a35a524a1625542015e67f5510bce},
intrahash = {981e8be5006d7a7a3b0abdb91c21ae8f},
issn = {1479-5876},
journal = {Journal of Translational Medicine},
keywords = {Carcinoma Disease Placenta Progression Proteins Tyrosine analysis protein response therapy},
number = 1,
pages = 32,
timestamp = {2010-02-05T11:28:55.000+0100},
title = {Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins},
url = {http://www.translational-medicine.com/content/5/1/32},
volume = 5,
year = 2007
}