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Maximal COX-2 immunostaining and clinical response to celecoxib and interferon alpha therapy in metastatic renal cell carcinoma
Article first published online: 20 DEC 2005
Copyright © 2005 American Cancer Society
Volume 106, Issue 3, pages 566–575, 1 February 2006
How to Cite
Rini, B. I., Weinberg, V., Dunlap, S., Elchinoff, A., Yu, N., Bok, R., Simko, J. and Small, E. J. (2006), Maximal COX-2 immunostaining and clinical response to celecoxib and interferon alpha therapy in metastatic renal cell carcinoma. Cancer, 106: 566–575. doi: 10.1002/cncr.21661
- Issue published online: 20 JAN 2006
- Article first published online: 20 DEC 2005
- Manuscript Accepted: 1 SEP 2005
- Manuscript Revised: 23 JUL 2005
- Manuscript Received: 5 MAY 2005
- National Comprehensive Cancer Network
- Pfizer, Inc.
- renal carcinoma;
- interferon alpha
Cyclooxygenase-2 (COX-2) plays a major role in the development of cancer through numerous mechanisms. COX-2 is expressed in the majority of renal cell carcinoma (RCC) tumors and correlates with stage, grade, and microvessel density. Based on potential additive or synergistic antitumor effects, interferon-alpha (IFNα) and celecoxib, an oral COX-2 inhibitor, were given to metastatic RCC patients in a Phase II trial.
Patients with untreated, metastatic RCC received IFNα 3 million units (MU) daily and celecoxib 400 mg orally (p.o.) twice daily continuously until disease progression or unacceptable toxicity. Pretreatment, paraffin-embedded RCC tumor samples were immunohistochemically stained for COX-2 expression and plasma basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were assayed to determine predictive or prognostic potential.
There were three partial responses among 25 patients treated (objective response rate, 12%; 95% confidence interval [CI], 3–31%). The observed median time to disease progression (TTP) for the entire cohort was 3.3 months. A significant association between maximal COX-2 staining and clinical response was observed: all patients who experienced an objective response demonstrated 3+ COX-2 tumor immunostaining (trend test: P = 0.03). Therapy was well tolerated without cardiac or other notable toxicity.
The addition of celecoxib to IFNα did not increase the objective response rate or TTP of this unselected cohort. Maximal COX-2 tumor immunostaining may identify RCC patents more likely to achieve clinical benefit with COX-2 inhibition in combination with IFNα. Further investigation of this combination in 3+ COX-2-overexpressing RCC tumors is warranted. Cancer 2006. © 2005 American Cancer Society.