Combination Of AVODART, Tamsulosin Provides Greater Benefit In Prostate Cancer Patients

Men with enlarged prostates who took a combination of two medications, AVODART (dutasteride) and tamsulosin, experienced significantly greater improvement in urinary symptoms than men prescribed either medication alone, GlaxoSmithKline said today.

The publication will mark the first time the full two-year results of the CombAT (Combination of Avodart and Tamsulosin) study, one of the largest clinical trials to date of men with enlarged prostate, have appeared in a major medical journal. Topline results were previously presented in September 2007 at the annual meeting of the Societe Internationale d'Urologie in Paris.

Enlarged prostate (also known as benign prostatic hyperplasia or BPH) is a progressive disease that affects 50 percent of men over the age of 50 and more than 90 percent of men over age 80.2 Common symptoms of enlarged prostate include frequent and/or urgent urination, which often is excessive at night, incomplete emptying, starting and stopping, and weak stream.

AVODART belongs to a medicine class known as 5-alpha reductase inhibitors (5-ARIs). Over time, Avodart shrinks the prostate, improves symptoms and arrests the enlarged prostate disease process. Tamsulosin is an alpha blocker, a class of medicines that relaxes muscles in the bladder and prostate. Alpha blockers provide rapid symptom improvement, but do not reduce prostate size or modify the disease process. The CombAT study is the first long-term assessment of the combination of AVODART and tamsulosin.

"CombAT is an important contribution to our evolving understanding of the management of enlarged prostate," according to Steven A. Kaplan, M.D., from Weill Cornell Medical College of Cornell University in New York City. Dr. Kaplan authored an editorial comment that will accompany the Journal of Urology publication of CombAT. "In this study, combination therapy yielded greater improvement in symptom score than either monotherapy within the first year of treatment, which appears to be a new finding. We then see in CombAT that this treatment difference holds true through Month 24."

In the CombAT study, male patients with moderate-to-severe enlarged prostate symptoms received placebo for four weeks and then were randomized to receive AVODART and tamsulosin as combination therapy, AVODART as monotherapy, or tamsulosin monotherapy (combination therapy, n=1610; AVODART, n=1623; tamsulosin, n=1611). The primary endpoint was the change in International Prostate Symptom Score (IPSS) score from baseline at Month 24 for combination therapy compared to each medication alone.

CombAT results showed at Month 24, that combination therapy demonstrated significantly greater symptom improvement for patients than either of the monotherapies (each comparison p<0.001). At Month 24, the mean decrease in IPSS from baseline was 6.2 points for combination therapy compared to 4.9 and 4.3 points for AVODART and tamsulosin, respectively.

All therapy regimens employed in the study appear to be generally well-tolerated. Although the total number of drug-related adverse events was significantly greater in the combination group compared with either monotherapy group, only 5% or less of men in each treatment group withdrew from the study as a result of these adverse events. The most common (greater than or equal to 2%) adverse events for combination therapy were erectile dysfunction (7.4%), retrograde ejaculation (4.2%), altered or decreased libido (3.4%), and ejaculation failure (2.4%). The most common adverse events for AVODART as monotherapy were erectile dysfunction (6.0%) and altered or decreased libido (2.8%), and for tamsulosin monotherapy was erectile dysfunction (3.8%).