title: Circulating endothelial progenitors and CXCR4-positive circulating endothelial cells are predictive markers for bevacizumab.
abstract: BACKGROUND
  Bevacizumab plus chemotherapy is a standard option in the treatment of metastatic colorectal cancer (mCRC). The aim of this study was to investigate the potential of circulating endothelial cell progenitors (CEPs) and phenotypical circulating endothelial cells (CECs) as surrogate markers of clinical outcome in mCRC patients to identify responders to bevacizumab in combination with chemotherapy.
  
  
  METHODS
  A total of 69 patients with measurable mCRC were enrolled in this prospective study. Whole blood samples were analyzed before initiation of treatment and on days 4 and 14. Phenotypical CECs and CEPs were then isolated and enumerated by using flow cytometry.
  
  
  RESULTS
  CEP levels of less than 0.04% on day 4 were significantly associated with longer progression-free survival (PFS) and overall survival (OS) (P < .001, P = .002, respectively) as compared with levels of 0.04% or more. In addition, CXCR4-positive CEC levels of less than 20% at baseline were significantly associated with longer PFS and OS as compared other indicators investigated (P < .001, P = .002, respectively).
  
  
  CONCLUSIONS
  Levels of CEPs on day 4 and proportion of CXCR4-positive CECs at baseline were correlated with the prognosis of bevacizumab combination chemotherapy, suggesting that these surrogate markers may play a core role in the selection of candidates for bevacizumab treatment.
authors.affiliation: Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsusaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishima
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Suenaga
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Terui
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kuniyoshi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013234:Stem Cells; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D019718:Receptors, CXCR4; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil