Source: Respiration  |  Posted 4 years ago

By Chris Berrie

BERLIN, GERMANY -- March 27, 2007 -- Combination treatment with the antimuscarinic agent tolterodine and the alpha-adrenergic receptor antagonist tamsulosin is significantly more effective than placebo and either treatment alone for men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BHP) and overactive bladder (OAB).

This randomised, placebo-controlled study was presented here on March 23[^]rd[] at the 22[^]nd[] Annual Congress of the European Association of Urology (EAU) by principal investigator David O. Sussman, MD, clinical associate professor, Department of Urology, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey, United States.

The symptoms included in LUTS relate to storage (urgency, frequency, nocturia, incontinence), voiding (slow stream, intermittent stream, hesitancy, straining, terminal dribble) and postmicturition (incomplete emptying, postmicturition dribble). These are often treated with alpha-adrenergic receptor antagonists due to their relation to BPH, hence targeting the prostate.

Symptoms of OAB are storage symptoms of urgency, with or without urgency urinary incontinence (UUI), usually with frequency and nocturia. With these symptoms, the antimuscarinic agents that reduce detrusor overactivity may be more effective than targeting the prostate.

Therefore, Dr. Sussman and colleagues assessed the efficacy of tolterodine and tamsulosin each as monotherapy and in combination for management of symptoms suggestive of both BPH and OAB.

A total of 851 men were enrolled who were 40 years or older and had total International Prostate Symptom Score of 12 or greater Quality of Life (QoL) item score of 3 or greater, at least moderate bother associated with their bladder symptoms, and micturition frequency for 8 hours or more each day and urgency of 3 or more episodes every 24 hours with or without UUI for 3 months or more.

Patients were randomised to 1 of 4 treatments as follows: 222 men received placebo; 217 received tolterodine 4 mg; 215 received tamsulosin 0.4 mg; and 225 received the combination of tolterodine plus tamsulosin. All patients were followed for 12 weeks.

Patient bladder diaries recorded urgency episodes/24 hours, micturations/24 hours, micturitions/night and UUI episodes/day were recorded over 5 days before baseline and weeks 1, 6 and 12.

Baseline characteristics of these treatment groups were not significantly different, and the ranges of their means were: urgency episodes/24 hours, 6.7-7.6; micturations/24 hours, 11.8-12.1; micturitions/night, 1.7-2.1; UUI episodes/day, 0.7-1.4; duration of OAB, 5-6 years; total and QoL IPSS, 19.5-20.1 and 4.6, respectively; maximum urinary flow rate (Q[_]max[]), 12.2-13.4 mL/second; and postvoid residual volume (PVR), 47.1-58.8 mL.

The primary efficacy endpoint of perception of treatment benefit at week 12 was significantly greater for the combination (80%) over placebo (62%, []P[] < .0001), tolterodine (65%, []P[] < .01) and tamsulosin (71%, []P[] < .05). The individual tolterodine and tamsulosin treatments did not achieve significant efficacy compared with placebo.

According to the patient bladder diaries, by week 12 the combination treatment achieved significant reductions over placebo for all variables ([]P[] < .05 - .001). Each agent alone achieved some transient significant improvements which were largely lost by week 12.

The drug combination provided significant effects over placebo for the remaining efficacy measures: reductions in sum urgency and OAB micturitions, and improvements in the OAB questionnaire terms of symptom bother, total health-related QoL, concern, coping and sleep. Similarly, the patients' perception of bladder condition was significantly improved. No specific effects were seen in either drug monotherapy group for these measures.

For the safety parameters relating to Q[_]max[] and PVR, there were no significant changes in any group; with incidence of acute urinary retention that required catheterisation was low in all groups.

"This study really looked at men who had combination symptoms, both storage and voiding symptoms, and clearly with this type of men, they did the best with combination therapy, therapy to treat their prostates, and therapy to treat their bladders," Dr. Sussman concluded.

This study was sponsored by Pfizer Inc.

[Presentation title: Effects of Tolterodine Extended Release and/or Tamsulosin on Bladder Diary Variables and Patient-Reported Outcomes in Men With Lower Urinary Tract Symptoms Including Overactive Bladder. Poster 1007]