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

Martin J. Edelman, Lydia Hodgson, Xiaofei Wang, Robert Christenson, Scott Jewell, Everett Vokes, Robert Kratzke

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1902-1906
Number of pages5
JournalJournal of Thoracic Oncology
Volume6
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • Celecoxib
  • Eicosanoid
  • Lung cancer
  • VEGF

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