title: Serum vascular endothelial growth factor and COX-2/5-LOX inhibition in advanced non-small cell lung cancer: Cancer and Leukemia Group B 150304.
abstract: BACKGROUND
  Eicosanoids, including PGE-2 and 5-HETE, can increase levels of plasma vascular endothelial growth factor (VEGF). Overexpression of COX-2 or 5-LOX increases levels of PGE-2 and 5-HETE, respectively. Elevated levels of VEGF are common in patients with non-small cell lung cancer (NSCLC). We prospectively measured VEGF in serum collected from patients enrolled in Cancer and Leukemia Group B 30203, a randomized phase II study of eicosanoid modulation in addition to chemotherapy in patients with advanced NSCLC, to determine whether these levels had prognostic significance and whether they correlated with COX-2 expression and/or responded to inhibition of COX-2 or 5-LOX.
  
  
  METHODS
  Pre- and post-treatment serum was collected from patients enrolled in CALGB 30203. Serum VEGF levels were determined using enzyme-linked immunosorbent assay methodology. Statistical analyses were performed to determine the correlation between pretreatment serum VEGF levels and time of overall survival. Pretreatment formalin fixed tissue was stained for 5-LOX and COX-2 by immunohistochemistry.
  
  
  RESULTS
  The median baseline VEGF level was 502 pg/ml (range, 55-3453 pg/ml). Dichotomized serum VEGF levels at median inversely correlated with survival time (p = 0.008), as did VEGF levels as a continuous variable in multivariate analysis (p = 0.035). VEGF levels were significantly correlated neither with baseline COX-2 expression (Pearson r = 0.1524, p = 0.271) nor with 5-LOX expression. Treatment with COX-2 or 5-LOX inhibitors did not alter the levels.
  
  
  CONCLUSIONS
  These data indicate that elevated serum VEGF is a negative prognostic variable in NSCLC. VEGF levels are neither correlated with baseline tumor COX-2 expression nor do they respond to COX-2 and/or 5-LOX inhibition plus chemotherapy.
authors.affiliation: University of Maryland Greenebaum Cancer Center, Baltimore, Maryland 21201, USA. medelman@umm.edu
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Lydia
authors.initials: L
authors.lastname: Hodgson
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Christenson
authors.forename: Scott
authors.initials: S
authors.lastname: Jewell
authors.forename: Everett
authors.initials: E
authors.lastname: Vokes
authors.forename: Robert
authors.initials: R
authors.lastname: Kratzke
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D011720:Pyrazoles; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D016190:Carboplatin; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D000093542:Gemcitabine