Open AccessPlasma Soluble VEGFR‐1 Is a Potential Dual Biomarker of Response and Toxicity for Bevacizumab with Chemoradiation in Locally Advanced Rectal Cancer
Author(s) -
Duda Dan G.,
Willett Christopher G.,
Ancukiewicz Marek,
Tomaso Emmanuelle,
Shah Mira,
Czito Brian G.,
Bentley Rex,
Poleski Martin,
Lauwers Gregory Y.,
Carroll Madeline,
Tyler Douglas,
Mantyh Christopher,
Shellito Paul,
Clark Jeffrey W.,
Jain Rakesh K.
Publication year - 2010
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2010-0029
Subject(s) - bevacizumab , medicine , colorectal cancer , vascular endothelial growth factor , oncology , biomarker , toxicity , neoadjuvant therapy , vascular endothelial growth factor a , chemotherapy , urology , cancer , vegf receptors , breast cancer , biology , biochemistry
We explored plasma and urinary concentrations of two members of the vascular endothelial growth factor (VEGF) family and their receptors as potential response and toxicity biomarkers of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer. The concentrations of VEGF, placental growth factor (PlGF), soluble VEGF receptor 1 (sVEGFR‐1), and sVEGFR‐2 were measured in plasma and urine at baseline and during treatment. Pretreatment values and changes over time were analyzed as potential biomarkers of pathological response to treatment as well as for acute toxicity in patients with locally advanced rectal cancer treated prospectively in 2002–2008 with neoadjuvant bevacizumab, 5‐fluorouracil, radiation therapy, and surgery in a phase I/II trial. Of all biomarkers, pretreatment plasma sVEGFR‐1—an endogenous blocker of VEGF and PlGF, and a factor linked with “vascular normalization”—was associated with both primary tumor regression and the development of adverse events after neoadjuvant bevacizumab and chemoradiation. Based on the findings in this exploratory study, we propose that plasma sVEGFR‐1 should be further studied as a potential biomarker to stratify patients in future studies of bevacizumab and/or cytotoxics in the neoadjuvant setting.