Trial Information

COX-2 Inhibitor Reduces Serum PSA Levels Might Predict a Lower Risk of Prostatic Cancer in Men With LUTS/BPH With an Elevated PSA Level

Study Procedure

- Male patients aged 40 years or older, having LUTS for at least 3 months (IPSS ≥ 8), a
serum PSA level ≥ 4 ng/ml, without a palpable prostatic nodule will be enrolled into
this prospective randomized trial to investigate whether COX-2 inhibitor can decrease
serum PSA level and acts as a biomarker to differentiate between chronic inflammation
and prostate cancer.

- Eligible subjects will be randomly assigned to the study and control groups at 2:1
ratio. The study group will receive doxazosin 4mg every day (QD) plus celecoxib 200mg
QD for 3 months and the control group will receive doxazosin 4 mg QD for 3 months.
Patients will be investigated for IPSS, total prostatic volume, transition zone index,
maximum flow rate, voided volume, postvoid residual, serum PSA, free PSA and serum
C-reactive protein (CRP) levels at baseline and 3 months after treatment. If the serum
PSA levels remained higher than 4 ng/ml, patients of either group will be advised to
receive prostatic biopsy for histopathological investigation.

- The prostatic biopsy will be advised at the end of the study in both groups of
patients. Ten prostatic biopsied strips will be sent to pathological department for
investigating the existence of prostatic cancer. The other two strips will be stored in
liquid nitrogen for further investigation of inflammatory biomarkers.

Data Analysis

- The efficacy evaluation will be performed on intention-to-treat populations (ITT) and
per-protocol populations (PPP) datasets while the safety evaluation will be performed
on ITT datasets. The primary conclusion will be made for the primary endpoint and
secondary endpoint on the ITT population.

Efficacy Endpoint Analysis

- Net change of each efficacy item will be analyzed by paired t-test between baseline and
post-treatment in the treatment group and controlled group. The net changes of each
efficacy item will be analyzed by ANOVA test to compare between treatment group and
controlled group. The global assessment by the patients will be analyzed by chi-square
test between the treatment and controlled group.

- All efficacy variables will be reported of respective point estimated and 95%
confidence interval. Comparison tests will be reported of respective p value.

Safety Endpoints

- Adverse events will be reported by both controlled and treatment groups and by
physiological systems as appropriate. Incidence of adverse events and the categories of
adverse event severity between treatments will be analyzed by Cochran-Mantel-Haenszel
test. The coding system used will be the Coding Symbols for a Thesaurus of Adverse
Reaction Terms (COSTART).

Changes in physical examinations will be displayed for each individual system.

- All statistical tests used will be two-tailed with α= 0.05.

Expected Results and Conclusion

- Chronic inflammation has been considered a possible but important factor to induce LUTS
and promote prostatic growth. PSA elevation is a sensitive but not specific sign for
prostatic cancer. In order to reduce the need for prostatic biopsy in patients with an
elevated serum PSA level, the results of this study might provide a simple way for
initial differential diagnosis of chronic inflammation from prostatic cancer. If serum
PSA can be reduced significantly after celecoxib therapy and the positive biopsy rate
of the following prostatic biopsy is lower than the control group, we might use this
treatment for the initial management of high PSA level in men with LUTS/BPH.
Furthermore, if chronic inflammation of the prostate can be reduced, the bothersome of
the LUTS as well as voiding condition might be improved. This result can be another
benefit for men who are suffering from LUTS and worried about surgical intervention.