Silodosin Shows Promise for Male Pelvic Pain Condition

Jill Stein

May 19, 2011

May 19, 2011 (Washington, DC) — Treatment with the highly selective alpha blocker silodosin seems to improve symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), according to phase 2 data presented here at the American Urological Association (AUA) 2011 Annual Scientific Meeting.

Results showed that 4 mg of once-daily silodosin was associated with a significant and modest but clinically meaningful reduction in symptoms, compared with placebo, in men with moderate to severe abacterial CP/CPPS. Treatment also improved disease-specific and general quality of life.

"Several types of agents are prescribed off-label in patients with CP/CPPS, including antibiotics, 5-alpha reductase inhibitors, gabapentinoids, and antiinflammatories. However, none has consistently shown efficacy in clinical studies," J. Curtis Nickel, MD, professor of urology at Queen's University and Kingston General Hospital in Ontario, Canada, told Medscape Medical News. "Our findings suggest that silodosin may help ease symptoms and improve quality of life in these patients. However, we would like to see these benefits further validated in follow-up trials."

In the study, 151 men were randomized to 12 weeks of daily treatment with silodosin 4 mg, silodosin 8 mg, or placebo. Silodosin is approved by the US Food and Drug Administration for use in men with benign prostatic hypertrophy associated with lower urinary tract symptoms (LUTS).

Inconsistent Results With Available Treatments

CP/CPPS is characterized by urogenital pain and variable LUTS in the absence of urinary tract infection (UTI), Dr. Nickel noted. The condition can be debilitating and has been shown to worsen disease-specific and general quality of life.

Alpha blockers, including terazosin, doxazosin, alfuzosin, and tamsulosin, which have proven efficacy in LUTS associated with benign prostatic hyperplasia, have been widely used for the treatment of CP/CPPS, Dr. Nickel explained. Their ability to block alpha 1–mediated signaling in the lower urinary tract and central nervous system has been thought to promote relaxation of the lower urinary tract, reduce peripheral and central neuropathy, and/or improve voiding functions, thereby improving CP/CPPS-related LUTS and pain. However, results using these agents have been inconsistent.

Phase 2 Study

Study participants were 18 years or older and had CP/CPPS, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of 15 or higher, and an NIH-CPSI pain score of at least 8. The NIH-CPSI is a 13-item questionnaire that has been widely validated for the assessment of symptom severity in men with CP/CPPS.

All men had experienced pain in the pelvic region for at least 3 months without a UTI, and had not received previous alpha-blocker therapy.

The primary efficacy measure was the change from baseline to week 12 in the NIH-CPSI total score. Silodosin 4 mg was associated with a significant decrease in total NIH-CPSI score, compared with placebo (mean change ± standard deviation, –12.1 ± 9.3 vs –8.5 ± 7.2; P = .0224).

Silodosin 4 mg daily was also associated with other improvements: reductions in urinary symptoms (–2.2 ± 2.7 vs –1.3 ± 3.0; P = .0102) and quality-of-life NIH-CPSI subscores (–4.1 ± 3.1 vs –2.7 ± 2.5; P = .0099); an increase in Short Form (SF)-12 physical component scores (4.2 ± 8.1 vs 1.7 ± 9.0 points; P = .0492); and a marked or moderate improvement on the Global Response Assessment scale (56% vs 29%; P = .0069).

Treatment with silodosin 8 mg daily provided no additional clinical benefit.

Silodosin 4 mg was well tolerated. The most common drug-related adverse event was retrograde ejaculation, which occurred in 14 of 52 (26.9%) patients receiving silodosin 4 mg, 18 of 45 (40%) receiving silodosin 8 mg, and 1 of 54 (1.9%) receiving placebo. Except for retrograde ejaculation, the frequency of treatment-related adverse effects for silodosin 4 mg was similar to that of placebo.

Dr. Nickel pointed out that the study is probably the only investigation to date to demonstrate a significant treatment-related benefit in general physical quality of life, as assessed by the SF-12 scale.

He also said that the findings are in line with some studies of alpha-blocker therapy, but are at odds with others. He suggested that the inconsistent outcomes reflect differences in study design, patient population, and choice of alpha blocker.

Finally, the urologist cautioned against extrapolating the results to patients who were heavily pretreated with alpha blockers, given that the study excluded patients who had undergone previous alpha-blocker treatment.

"The finding that the superselective alpha blocker silodosin significantly improved voiding symptoms in men with a history of interstitial cystitis or chronic pelvic pain is encouraging because these men report significant suffering and have often failed multiple therapies, like tricyclic antidepressants, anticholinergics, and pain medications, or complain of the treatment-related side effects that make them stop treatment," Tomas L. Griebling, MD, MPH, AUA spokesperson, and associate professor and vice chair of the Department of Urology at the University of Kansas Medical Center in Kansas City, told Medscape Medical News. "It's clear that we need to expand our options, and this drug may benefit some patients."

He added that the favorable effect of silodosin might be the result of its "superselectivity."

"There are several different receptor subtypes for alpha-adrenergic medications. This one is specifically selective for subtype 1a, which we think is involved in smooth muscle relaxation and contraction."

Funding for the 32-center study was provided by Watson Laboratories, Inc. Dr. Nickel reports being a consultant and investigator for Watson Laboratories. Dr. Griebling has disclosed no relevant financial relationships.

American Urological Association (AUA) 2011 Annual Scientific Meeting: Abstract 1433. Presented May 17, 2011.

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