title: Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy.
abstract: OBJECTIVE
  The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo.
  
  
  METHODS
  In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks.
  
  
  RESULTS
  VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence interval (CI) 0.43-0.95], p=0.028).
  
  
  CONCLUSIONS
  Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.
authors.affiliation: Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Sweden. sverre.sorenson@liu.se
authors.forename: Sverre
authors.initials: S
authors.lastname: Sörenson
authors.forename: Helena
authors.initials: H
authors.lastname: Fohlin
authors.forename: Andrea
authors.initials: A
authors.lastname: Lindgren
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindskog
authors.forename: Bengt
authors.initials: B
authors.lastname: Bergman
authors.forename: Christer
authors.initials: C
authors.lastname: Sederholm
authors.forename: Lars
authors.initials: L
authors.lastname: Ek
authors.forename: Kristina
authors.initials: K
authors.lastname: Lamberg
authors.forename: Birgitta
authors.initials: B
authors.lastname: Clinchy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D000068579:Celecoxib; D005260:Female; D006801:Humans; D007118:Immunoassay; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011720:Pyrazoles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D000068579:Celecoxib