Journal of Clinical Immunology

, Volume 31, Issue 4, pp 690–698 | Cite as

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
Article

Abstract

Introduction

Cycloxygenase-2 (COX-2) is an enzyme involved in prostaglandin E2 (PGE2) 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-α 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 PGE2 levels, and these patients demonstrated less PGE2 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-α 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.

Keywords

Interferon-α celecoxib renal cell carcinoma immunotherapy T-regulatory cells 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Anita Schwandt
    • 1
  • Jorge A. Garcia
    • 1
  • Paul Elson
    • 2
  • Jeanie Wyckhouse
    • 1
  • James H. Finke
    • 3
  • Joanna Ireland
    • 3
  • Pierre Triozzi
    • 1
  • Ming Zhou
    • 4
  • Robert Dreicer
    • 1
  • Brian I. Rini
    • 1
  1. 1.Department of Solid Tumor OncologyCleveland Clinic Taussig Cancer InstituteClevelandUSA
  2. 2.Department of Quantitative Health SciencesCleveland ClinicClevelandUSA
  3. 3.Department of ImmunologyLerner Research Institute, Cleveland ClinicClevelandUSA
  4. 4.Department of PathologyCleveland ClinicClevelandUSA

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