title: Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib.
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKI) have enriched the therapeutic options in patients with renal cell carcinoma (RCC), which frequently induce morphological changes in tumors. However, only little is known about the biological activity of TKI. Circulating endothelial cells (CEC) have been associated with endothelial damage and, hence, may serve as a putative marker for the biological activity of TKI. The main objective of our study was to evaluate the predictive value of CEC, monocytes, and soluble vascular endothelial growth factor receptor (sVEGFR)-2 in RCC patients receiving sunitinib treatment.
  
  
  METHODS
  Analyses of CEC, monocytes, and sVEGFR-2 were accomplished for twenty-six consecutive patients with metastatic RCC who received treatment with sunitinib (50 mg, 4 wks on 2 wks off schedule) at our institution in 2005 and 2006.
  
  
  RESULTS
  In RCC patients CEC are elevated to 49 ± 44/ml (control 8 ± 8/ml; P = 0.0001). Treatment with sunitinib is associated with an increase in CEC within 28 days of treatment in patients with a Progression free survival (PFS) above the median to 111 ± 61 (P = 0.0109), whereas changes in patients with a PFS below the median remain insignificant 69 ± 61/ml (P = 0.1848). Monocytes and sVEGFR2 are frequently altered upon sunitinib treatment, but fail to correlate with clinical response, defined by PFS above or below the median.
  
  
  CONCLUSIONS
  Sunitinib treatment is associated with an early increase of CEC in responding patients, suggesting superior endothelial cell damage in these patients as a putative predictive biomarker.
authors.affiliation: Hannover Medical School, Germany. Gruenwald.Viktor@MH-Hannover.de
authors.forename: Viktor
authors.initials: V
authors.lastname: Gruenwald
authors.forename: Gernot
authors.initials: G
authors.lastname: Beutel
authors.forename: Susanne
authors.initials: S
authors.lastname: Schuch-Jantsch
authors.forename: Christoph
authors.initials: C
authors.lastname: Reuter
authors.forename: Philipp
authors.initials: P
authors.lastname: Ivanyi
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Marion
authors.initials: M
authors.lastname: Haubitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005858:Germany; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000473:pathology; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D000077210:Sunitinib; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib