Abstract
Introduction Cycloxygenase-2 (COX-2) is an enzyme involved in prostaglandin E2 (PGE 2) synthesis associated with higher renal cell carcinoma stage. COX-2 inhibition enhances interferon (IFN-α) anti-tumor immune effects in pre-clinical models. A phase II trial of celecoxib and IFN-a in a targeted population of metastatic renal cell carcinoma patients with maximal COX-2 expression was conducted. Methods Cytokine-naive metastatic renal cell carcinoma patients with tumors expressing ≥10% maximal COX-2 staining by immunohistochemistry received IFN-α 5 million units daily and celecoxib 400 mg orally twice daily in an open-label, single-arm phase II trial. Results There were 3 partial responses among 17 patients (objective response rate 18%; 95% confidence interval, 4- 43%). Time to progression was 5.6 months. Increased tumor staining 3+ for COX-2 was associated with increased baseline peripheral blood PGE 2 levels, and these patients demonstrated less PGE 2 decrease with therapy. Patients with more 3+ COX-2 staining had significantly more CD3 + (p=0.004) and CD4 + (p=0.002) IFN-γ T cells at baseline and a significantly greater decrease in these cells with therapy. Discussion Celecoxib plus IFN-a in renal cell carcinoma (RCC) patients with maximally staining COX-2 tumors does not significantly enhance overall response rates over IFN monotherapy. Conclusion COX-2-expressing RCC demonstrates inherent immunosuppression. COX-2 inhibition with IFN results in minimal immunomodulation and no augmented clinical activity in RCC.
Original language | English (US) |
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Pages (from-to) | 690-698 |
Number of pages | 9 |
Journal | Journal of Clinical Immunology |
Volume | 31 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2011 |
Keywords
- Celecoxib
- Immunotherapy
- Interferon-α
- Renal cell carcinoma
- T-regulatory cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology