Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer.
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.
Duda
Dan G
DG
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Willett
Christopher G
CG
Ancukiewicz
Marek
M
di Tomaso
Emmanuelle
E
Shah
Mira
M
Czito
Brian G
BG
Bentley
Rex
R
Poleski
Martin
M
Lauwers
Gregory Y
GY
Carroll
Madeline
M
Tyler
Douglas
D
Mantyh
Christopher
C
Shellito
Paul
P
Clark
Jeffrey W
JW
Jain
Rakesh K
RK
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D020360:Neoadjuvant Therapy; D012004:Rectal Neoplasms / Q000097:blood* / Q000628:therapy* / Q000652:urine; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D040281:Vascular Endothelial Growth Factor Receptor-1; D005472:Fluorouracil