Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men with Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers

Emmanuel S. Antonarakis, Elisabeth I. Heath, Janet R. Walczak, William G. Nelson, Helen Fedor, Angelo M. De Marzo, Marianna L. Zahurak, Steven Piantadosi, Andrew J. Dannenberg, Robin T. Gurganus, Sharyn D. Baker, Howard L. Parnes, Theodore L. DeWeese, Alan W. Partin, Michael A. Carducci

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy. Patients and Methods: Patients with localized prostate cancer and Gleason sum ≥ 7, prostate-specific antigen (PSA) ≥ 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance. Results Seventy-three patients consented, and 64 were randomly assigned and included in the intentionto-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities. Conclusion Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies.

Original languageEnglish (US)
Pages (from-to)4986-4993
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number30
DOIs
StatePublished - Oct 20 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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