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 language | English (US) |
|---|---|
| Pages (from-to) | 1902-1906 |
| Number of pages | 5 |
| Journal | Journal of Thoracic Oncology |
| Volume | 6 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2011 |
Bibliographical note
Funding Information:University of Oklahoma, Oklahoma, OK–Shubham Pant, MD, supported by CA37447
Funding Information:
Nevada Cancer Research Foundation CCOP, Las Vegas, NV–John A. Ellerton, MD, supported by CA35421
Funding Information:
The research for CALGB 15034 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Monica M. Bertagnolli, MD, Chair) and to the CALGB Statistical Center (Daniel J. Sargent, PhD, CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.
Funding Information:
University of North Carolina at Chapel Hill, Chapel Hill, NC–Thomas C. Shea, MD, supported by CA47559
Funding Information:
University of Vermont, Burlington, VT–Steven M Grunberg, MD, supported by CA77406
Funding Information:
University of Maryland Greenebaum Cancer Center, Baltimore, MD–Martin Edelman, MD, supported by CA31983
Funding Information:
University of Missouri/Ellis Fischel Cancer Center, Columbia, MO–Michael C Perry, MD, supported by CA12046
Funding Information:
University of Chicago, Chicago, IL–Hedy L Kindler, MD, supported by CA41287
Keywords
- Celecoxib
- Eicosanoid
- Lung cancer
- VEGF
