Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer

Dan G. Duda, Christopher G. Willett, Marek Ancukiewicz, Emmanuelle di Tomaso, Mira Shah, Brian G. Czito, Rex Bentley, Martin Poleski, Gregory Y. Lauwers, Madeline Carroll, Douglas Tyler, Christopher Mantyh, Paul Shellito, Jeffrey W. Clark, Rakesh K. Jain

Research output: Contribution to journalArticle

65 Scopus citations

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-2were 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.

Original languageEnglish (US)
Pages (from-to)577-583
Number of pages7
JournalOncologist
Volume15
Issue number6
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

    Fingerprint

Keywords

  • Bevacizumab
  • Biomarker
  • Chemoradiation
  • Rectal cancer
  • Toxicity
  • sVEGFR-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Duda, D. G., Willett, C. G., Ancukiewicz, M., di Tomaso, E., Shah, M., Czito, B. G., Bentley, R., Poleski, M., Lauwers, G. Y., Carroll, M., Tyler, D., Mantyh, C., Shellito, P., Clark, J. W., & Jain, R. K. (2010). Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer. Oncologist, 15(6), 577-583. https://doi.org/10.1634/theoncologist.2010-0029