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Maximal COX‐2 immunostaining and clinical response to celecoxib and interferon alpha therapy in metastatic renal cell carcinoma
Author(s) -
Rini Brian I.,
Weinberg Vivian,
Dunlap Sarah,
Elchinoff Alexandra,
Yu Nancy,
Bok Robert,
Simko Jeffery,
Small Eric J.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21661
Subject(s) - medicine , renal cell carcinoma , celecoxib , cancer , immunostaining , oncology , gastroenterology , pathology , immunohistochemistry
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.