Originally published as JCO Early Release 10.1200/JCO.2009.21.9410 on August 31 2009

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

From the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Brady Urological Institute at Johns Hopkins, Baltimore; National Cancer Institute, Bethesda, MD; Karmanos Cancer Institute, Wayne State University, Detroit, MI; Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA; and Weill Cornell Medical College, New York, NY.

Corresponding author: Michael A. Carducci, MD, Prostate Cancer Research Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, CRB1 1M59, 1650 Orleans St, Baltimore, MD 21231; e-mail: carducci{at}jhmi.edu.

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 intention-to-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.

Supported by National Cancer Institute Grant No. N01-CN-95000-46 (M.A.C.) and by Pfizer (M.A.C).

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00022399 [ClinicalTrials.gov] .

See accompanying editorial on page 4937

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