title: Evaluation of potentially predictive markers for anti-angiogenic therapy with sunitinib in recurrent ovarian cancer patients.
abstract: BACKGROUND
  In ovarian cancer, new therapeutic strategies are needed because the vast majority of patients develop a recurrence and resistance to platinum derivates. Attached to the AGO-OVAR2.11 study investigating the multityrosine kinase inhibitor sunitinib in recurrent platinum refractory ovarian cancers, this translational research project assesses the potential value of serum vascular endothelial growth factor (VEGF), soluble VEGF receptor-3 (sVEGFR-3), and angiopoietin-2 (Ang-2) levels for progression-free survival (PFS).
  
  
  METHODS
  Longitudinal serum samples were taken while the patient was on study drugs. Serum concentration of VEGF, sVEGFR-3, and Ang-2 was determined by ELISA. The slope of the markers was correlated to the PFS.
  
  
  RESULTS
  Patients showing a decrease in VEGF concentration had a median PFS of 10.5 months [confidence interval (CI), 2.89-12.25] compared to 2.9 months (CI, 1.48-5.32) in the case of an increase (P = .17). The stratified log-rank test showed a trend for longer PFS if a decrease of Ang-2 was observed (P = .089). Dichotomized in absolute decrease or increase, the PFS was 8.4 months (CI, 2.89-12.26) versus 2.7 months (CI, 1.05-5.32), respectively. Patients with a reduction of the sVEGFR-3 concentration had a median PFS of 4.76 months (CI 2.86-10.65) versus 8.61 months (CI, 1.05-not estimable) in patients with an increase of sVEGFR-3. This observation was statistically not significant in the log-rank test (P = .81).
  
  
  CONCLUSIONS
  Ang-2 could potentially identify a patient population that might have a better PFS when under anti-angiogenic treatment, like the tyrosine kinase inhibitor sunitinib.
authors.affiliation: Department of Gynecological Oncology, University Medical Center Aachen, RWTH, Aachen, Germany.
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Bauerschlag
authors.forename: Felix
authors.initials: F
authors.lastname: Hilpert
authors.forename: Werner
authors.initials: W
authors.lastname: Meier
authors.forename: Jörn
authors.initials: J
authors.lastname: Rau
authors.forename: Ivo
authors.initials: I
authors.lastname: Meinhold-Heerlein
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.forename: Andreas
authors.initials: A
authors.lastname: Dubois
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Christian
authors.initials: C
authors.lastname: Schem
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Oberg
authors.forename: Klaus
authors.initials: K
authors.lastname: Baumann