期刊
CANCER
卷 106, 期 3, 页码 566-575出版社
JOHN WILEY & SONS INC
DOI: 10.1002/cncr.21661
关键词
renal carcinoma; COX-2; VEGF; bFGF; interferon alpha
类别
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 (IFN alpha) and celecoxib, an oral COX-2 inhibitor, were given to metastatic RCC patients in a Phase 11 trial. METHODS. Patients with untreated, metastatic RCC received IFNa 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 IFN alpha 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 IFN alpha. Further investigation of this combination in 3+ COX-2-overexpressing RCC tumors is warranted.
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