Serum vascular endothelial growth factor and COX-2/5-LOX inhibition in advanced non-small cell lung cancer: Cancer and Leukemia Group B 150304

J Thorac Oncol. 2011 Nov;6(11):1902-6. doi: 10.1097/JTO.0b013e31822a7383.

Abstract

Introduction: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arachidonate 5-Lipoxygenase / chemistry*
  • Arachidonate 5-Lipoxygenase / metabolism
  • Biomarkers, Tumor / blood*
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology
  • Celecoxib
  • Cyclooxygenase 2 / chemistry*
  • Cyclooxygenase 2 / metabolism
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / enzymology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Pyrazoles / administration & dosage
  • Sulfonamides / administration & dosage
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Biomarkers, Tumor
  • Pyrazoles
  • Sulfonamides
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Deoxycytidine
  • gemcitabine
  • Carboplatin
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Celecoxib