title: Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Dan G
authors.initials: DG
authors.lastname: Duda
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Willett
authors.forename: Marek
authors.initials: M
authors.lastname: Ancukiewicz
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: di Tomaso
authors.forename: Mira
authors.initials: M
authors.lastname: Shah
authors.forename: Brian G
authors.initials: BG
authors.lastname: Czito
authors.forename: Rex
authors.initials: R
authors.lastname: Bentley
authors.forename: Martin
authors.initials: M
authors.lastname: Poleski
authors.forename: Gregory Y
authors.initials: GY
authors.lastname: Lauwers
authors.forename: Madeline
authors.initials: M
authors.lastname: Carroll
authors.forename: Douglas
authors.initials: D
authors.lastname: Tyler
authors.forename: Christopher
authors.initials: C
authors.lastname: Mantyh
authors.forename: Paul
authors.initials: P
authors.lastname: Shellito
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D040281:Vascular Endothelial Growth Factor Receptor-1; D005472:Fluorouracil