A recent Phase II trial of the COX-2 inhibitor celecoxib (Celebrex/Pfizer) showed that this agent “had no effect on intermediate biomarkers of prostate carcinogenesis.”
The enzyme cyclooxygenase-2 (COX-2) has been looked at as a potential target for the prevention of several forms of cancer, including prostate cancer. Antonarakis et al. have recently reported results from a randomized, double-blind, Phase II clinical trial designed to investigate the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at the time of radical prostatectomy.
The trial enrolled patients with localized prostate cancer which met the following criteria: Gleason sum ≥ 7, PSA level ≥ 15 ng/ml, clinical stage T2b or greater, or any combination with greater than 45 percent risk of capsular penetration. The patients were randomly assigned to treatment with celecoxib 400 mg twice daily or a placebo (sugar pill) for 4 to 6 weeks before their radical prostatectomy.
The primary endpoint of the trial was the difference in prostatic prostaglandin levels between the two groups. Secondary endpoints were differences in the expression of the COX-1 and COX-2 enzymes; oxidized DNA bases; and markers of proliferation, apoptosis, and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary trial endpoints were drug safety and compliance.
The results of the trial showed that:
- 73 patients agreed to participate in the trial, and 64 were randomly assigned and included in the intent-to-treat analysis.
- There were no treatment-related differences in any of the primary or secondary outcomes.
- Tumor tissue examined after surgery had significantly lower levels of expression of the COX-2 enzyme than benign tissue from the same prostate, and significantly higher levels of the proliferation marker Ki-67.
- Celecoxib was measurable in the prostate tissue of patients on treatment, demonstrating that celecoxib reached its target.
- Treatment with celecoxib was safe and resulted in only mild (grade 1) side effects.
The authors conclude that, “Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels.” They go on to state that, “We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies.”
Since we already know that the COX-2 inhibitors are associated with a range of potentially serious cardiovascular side effects (which led to the withdrawal of Vioxx from the market in the USA some years ago), the use of a COX-2 inhibitor to prevent prostate cancer would have needed to demonstrate massive potential impact on risk for prostate cancer to overcome the potential for known side effects. This study would certainly appear to suggest that the potential is small, and far from massive!
Filed under: Drugs in development, Prevention Tagged: | celecoxib, COX-2, Prevention
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