Clinical and immunomodulatory effects of celecoxib plus Interferon-Alpha in Metastatic Renal Cell Carcinoma patients with COX-2 tumor immunostaining

Anita Schwandt, Jorge A. Garcia, Paul Elson, Jeanie Wyckhouse, James H. Finke, Joanna Ireland, Pierre Triozzi, Ming Zhou, Robert Dreicer, Brian I. Rini

Research output: Contribution to journalArticle

13 Scopus citations

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 languageEnglish (US)
Pages (from-to)690-698
Number of pages9
JournalJournal of Clinical Immunology
Volume31
Issue number4
DOIs
StatePublished - Aug 1 2011

Keywords

  • Celecoxib
  • Immunotherapy
  • Interferon-α
  • Renal cell carcinoma
  • T-regulatory cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Schwandt, A., Garcia, J. A., Elson, P., Wyckhouse, J., Finke, J. H., Ireland, J., Triozzi, P., Zhou, M., Dreicer, R., & Rini, B. I. (2011). Clinical and immunomodulatory effects of celecoxib plus Interferon-Alpha in Metastatic Renal Cell Carcinoma patients with COX-2 tumor immunostaining. Journal of Clinical Immunology, 31(4), 690-698. https://doi.org/10.1007/s10875-011-9530-x