The Clinical Efficacy of Non-steroidal Anti-inflammation Drugs in Patients With Benign Prostatic Hyperplasia

• The changes of voiding frequencies after medications [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• The changes of 'ICS male questionnaire-short form' after medications [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Patient perception of treatment benefit questionnaire [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• The changes of 'patient perception of bladder condition' after medications [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• The changes of maximum flow rate and postvoid residuals after medications [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• The changes of serum PSA levels after medications [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• The changes of WBC counts on the expressed prostatic secretions after medications [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Complications [ Time Frame: During all study periods ] [ Designated as safety issue: Yes ]

Non-steroidal Anti-inflammation Drugs can effectively reduce the lower urinary tract symptoms from benign prostatic hyperplasia

• Drug: selective alpha 1-blockers
  Continued medication that the patient had before the enrollment of this study (tamsulosin 0.2mg, alfuzosin 10mg, doxazosin 4, 8mg, or terazosin 2-10mg daily for 8 weeks)
  Other Names:

  • tamsulosin
  • alfuzosin
  • doxazosin
  • terazosin
• Drug: celecoxib
  200mg daily for 8 weeks
  Other Name: celecoxib
• Drug: alpha-blocker and NSAID
  amsulosin 0.2mg, alfuzosin 10mg, doxazosin 4, 8mg, or terazosin 2-10mg daily for 8 weeks and celecoxib 200mg daily for 8 weeks
  Other Names:

  • tamsulosin and celecoxib
  • alfuzosin and celecoxib
  • doxazosin and celecoxib
  • terazosin and celecoxib

• Active Comparator: Alpha-blocker
  Alpha-blocker only
  Intervention: Drug: selective alpha 1-blockers
• Active Comparator: NSAID
  NSAID only
  Intervention: Drug: celecoxib
• Experimental: alpha-blocker and NSAID
  Combination treatment of alpha-blocker and NSAID
  Intervention: Drug: alpha-blocker and NSAID

• Kramer G, Steiner GE, Handisurya A, Stix U, Haitel A, Knerer B, Gessl A, Lee C, Marberger M. Increased expression of lymphocyte-derived cytokines in benign hyperplastic prostate tissue, identification of the producing cell types, and effect of differentially expressed cytokines on stromal cell proliferation. Prostate. 2002 Jun 1;52(1):43-58.
• Untergasser G, Madersbacher S, Berger P. Benign prostatic hyperplasia: age-related tissue-remodeling. Exp Gerontol. 2005 Mar;40(3):121-8. Epub 2005 Jan 22. Review.
• Lee KL, Peehl DM. Molecular and cellular pathogenesis of benign prostatic hyperplasia. J Urol. 2004 Nov;172(5 Pt 1):1784-91. Review.
• Handisurya A, Steiner GE, Stix U, Ecker RC, Pfaffeneder-Mantai S, Langer D, Kramer G, Memaran-Dadgar N, Marberger M. Differential expression of interleukin-15, a pro-inflammatory cytokine and T-cell growth factor, and its receptor in human prostate. Prostate. 2001 Dec 1;49(4):251-62.
• Kakehi Y, Segawa T, Wu XX, Kulkarni P, Dhir R, Getzenberg RH. Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia. Prostate. 2004 Jun 1;59(4):351-6.
• Steiner GE, Newman ME, Paikl D, Stix U, Memaran-Dagda N, Lee C, Marberger MJ. Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate. 2003 Aug 1;56(3):171-82.
• Wang W, Bergh A, Damber JE. Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium. Prostate. 2004 Sep 15;61(1):60-72.
• Kramer G, Marberger M. Could inflammation be a key component in the progression of benign prostatic hyperplasia? Curr Opin Urol. 2006 Jan;16(1):25-9. Review.
• Rohrmann S, De Marzo AM, Smit E, Giovannucci E, Platz EA. Serum C-reactive protein concentration and lower urinary tract symptoms in older men in the Third National Health and Nutrition Examination Survey (NHANES III). Prostate. 2005 Jan 1;62(1):27-33.
• Araki T, Yokoyama T, Kumon H. Effectiveness of a nonsteroidal anti-inflammatory drug for nocturia on patients with benign prostatic hyperplasia: a prospective non-randomized study of loxoprofen sodium 60 mg once daily before sleeping. Acta Med Okayama. 2004 Feb;58(1):45-9.

Inclusion Criteria:

• Who had the treatment of BPH with alpha-1 blockers for more than 3 months
• Who have the IPSS(International Prostatic Symptom Score) >= 15
• Who have the maximum flow rate(Qmax) < 15 with voided volume > 150mL
• Who have the PPBC(patient's perception of bladder condition) >= 3 (The PPBC was assessed by the use of a six point ordered categorical scale(1-6 point). The higher score means the higher bother)
• Who had the PSA level < 4 ng/mL within 6 months (But, the patient who are revealed not to have prostate cancer by prostate biopsy can be included even if he had PSA level of 4-10 ng/mL)
• Who underwent the transrectal ultrasound of prostate within 6 months
• Who can understand this study and can give the informed consent

Exclusion Criteria:

• Who had regular intake of 5-alpha reductase inhibitor or NSAID within 6 months before screening
• Who have peptic ulcer and/or asthma
• Who have urologic malignancies such as prostate cancer and bladder cancer
• Who have urethral strictures, large bladder diverticuli, and bladder neck contractures
• Who had surgical treatment for BPH
• Who have histories of bladder and/or urethra
• Who have serum PSA level more than 10 ng/ml
• Who have histories of orthostatic hypotension
• Who have serum creatinine level more than 2.0 mg/dl
• Who have serum ALT and/or AST level more than 1.5 times of normal upper limit
• Who have heart failure
• Who have histories of bacterial prostatitis within 1 year
• Who have histories of active urinary tract infection within 1 month
• Who have histories of the biopsy of bladder and prostate within 1 month
• Who are unable to void
• Who use pads because of incontinences
• Who have hypersensitivities for alpha blockers that include quinazoline, NSAID, aspirin, sulfonamide
• Who have histories of unstable angina, myocardial infarction, and cerebrovascular accident within 6 months
• Who have neurogenic bladder due to multiple sclerosis, Parkinson's disease, Spinal injuries and etc.
• Who have thinking disturbances
• Who have histories of abuses of alcohol and/or other drugs
• Who seem to be not fit to this study by the decision of investigators