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Two-Drug Therapy Could Become New Standard of Care for Moderate-to-Severe Male Overactive Bladder

Tolterodine Plus Tamsulosin Works Better Than Either Drug Alone

NEW YORK, NY -- November 20, 2006 -- A major clinical trial finds that a combination of two common medications -- tolterodine (Detrol LA) and tamsulosin (Flomax) -- works better than either drug alone for men struggling with lower urinary tract symptoms, including tough-to-treat overactive bladder (OAB).

"A full 80% of men with moderate-to-severe OAB -- which is characterized by symptoms such as urgent and frequent urination -- who received these two drugs together reported a real benefit within three months of treatment," says the study's lead author, Dr. Steven A. Kaplan, professor of urology at Weill Cornell Medical College and attending urologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City. "In contrast, patients receiving either tolterodine or tamsulosin alone reported improvements that were little more than those seen by patients on placebo," he adds.

"Based on these findings, we believe that a combination of medications such as tolterodine/tamsulosin may become a new 'gold standard' for the treatment of bothersome moderate-to-severe overactive bladder symptoms in this patient population," Dr. Kaplan says.

The NewYork-Presbyterian/Weill Cornell expert will present the findings Tuesday, Nov. 14, at 10 a.m., at a JAMA news briefing in New York City. The study will be published in the Nov. 15 edition of the Journal of the American Medical Association, a special issue devoted to men's health.

Experts estimate that 10 million American men aged 40 and over suffer from overactive bladder. The current standard of care involves the use of an "antimuscarinic" drug such as tolterodine to help alleviate OAB symptoms. Antimuscarinics help regulate bladder contractions through their effects on the bladder's detrusor muscle.

In many cases, doctors may also suspect that an enlarged prostate ("benign prostatic hyperplasia" or BPH) is an underlying cause of OAB. In those instances, they will prescribe an "alpha-adrenergic receptor antagonist" drug such as tamsulosin, which eases symptoms through its effect on prostate muscle tone.

"The problem is that men with OAB and enlarged prostate can have an overactive bladder without it being caused by this prostatic condition, so they don't respond to drugs such as tamsulosin" Dr. Kaplan notes. "Likewise, some patients do not respond to tolterodine alone, either."

However, urologists have reported anecdotal success in using both of these agents together for moderate-to-severe male OAB. In this study, Dr. Kaplan and colleagues at NewYork-Presbyterian/Weill Cornell -- along with researchers at the University of Texas Southwestern Medical Center and the Medical University of South Carolina -- tested this approach in a double-blinded, randomized clinical trial involving more than 850 patients treated at 95 urology clinics across the U.S. The study was funded by Pfizer Inc., the maker of Detrol LA.

Patients were all 40 years of age or older (average age 62) with symptoms suggestive of an enlarged prostate and a history of moderate-to-severe overactive bladder, including a frequent urination and urgency with or without incontinence. Patients with any history of prostate surgery or prostate cancer were excluded from the study.

The 12-week, double-blinded, placebo-controlled study randomized participants into one of four treatment groups: one arm (217 patients) received a once-daily 4 mg dose of tolterodine, a second arm (215 pts.) received 0.4 mg of tamsulosin once per day, a third group (225 pts.) was given both drugs in combination, while a fourth group (222 pts.) received a daily placebo.

The researchers had participants record changes in daily symptoms -- items such as frequency of urinary incontinence -- in special "bladder diaries." They also questioned each participant on their "perception of treatment benefit" at weeks 1, 6 and 12. Urinary flow rates and volume were also assessed at baseline and at week 12 via flowmeter and ultrasound.

The result: "We found a marked improvement in OAB for patients taking both drugs together, with 80% reporting a real treatment benefit compared to 62% for those on placebo," Dr. Kaplan reports. "In contrast, treatment benefit rates for monotherapy did not rise much above placebo -- 71% for patients taking tamsulosin and 65% for those given tolterodine monotherapy."

Compared to monotherapy, tolterodine/tamsulosin in combination achieved significantly higher rates of symptom reduction in terms of urgency urinary incontinence, urgency episodes without incontinence, voiding per 24 hours, and night voiding. Patients on the two-drug therapy also reported significant improvement in their quality of life compared to monotherapy or placebo, the researchers added.

Each of the three drug regimens was well-tolerated, with dry mouth being the most frequently reported symptom. Patients on combination therapy did report a higher incidence of dry mouth than those taking monotherapy (21% vs. 7%, respectively). "The reasons for this increase in dry mouth remain unclear and require further study," Dr. Kaplan says. "We have some evidence, however, that taking the drugs just before bed, rather than after dinner as in this study, could reduce risks for these and other adverse effects."

The bottom line, according to Dr. Kaplan, is that the findings "strongly support the use of these two medications in combination as safe and effective therapy for men with moderate-to-severe lower urinary tract symptoms, including OAB."

"For many men who are bothered by OAB, monotherapy -- which targets one potential cause of the illness -- is simply not enough to ease symptoms," he says. "In that context, the use of tolterodine and tamsulosin together may work much better, since it tackles the problem on multiple fronts."

Co-researchers include senior researcher Dr. Zhonghong Guan of Pfizer Inc., New York City; Dr. Tamara Bavendam and Martin Carlsson, also of Pfizer; Dr. Claus G. Roehrborn of the University of Texas Southwestern Medical Center, Dallas; and Dr. Eric S. Rovner of the Medical University of South Carolina, in Charleston.


SOURCE: NewYork-Presbyterian Hospital/Weill Cornell Medical Center

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