Therapy combination superior in high-risk BPH patients

June 1, 2008

The combination of dutasteride (Avodart) and tamsulosin (Flomax) provides significantly greater improvement in International Prostate Symptom Score (IPSS) and patient-reported quality of life than either therapy alone in men with BPH who are at increased risk of progression.

Key Points

That finding comes from a 2-year analysis of data from the Combination of Avodart and Tamsulosin (CombAT) trial, an ongoing, multicenter, randomized, double-blind, parallel-group study involving nearly 5,000 men and designed to last 4 years.

The data also showed that monotherapy with dutasteride, a 5-alpha-reductase inhibitor, was significantly superior to the alpha-blocker tamsulosin for IPSS reduction in men <65 years of age with IPSS ≥16, quality of life score ≥4, and with larger baseline prostate volumes and serum PSAs.

"What was interesting, though, was the fact that for the first time, we see a better IPSS response with the 5-alpha-reductase inhibitor than we did with the alpha-blocker," he said.

Indeed, dutasteride outperformed tamsulosin in terms of IPSS reduction as early as 15 months into the trial. That defies conventional wisdom among urologists, which holds that alpha-blockers have a rapid onset, and are therefore best for quickly treating symptoms.

"In patients with larger glands, 5-alpha-reductase inhibitors are not only good for disease modification, but also for superior symptom relief and flow-rate improvement," said co-author Claus Roehrborn, MD, professor and chairman of urology, University of Texas Southwestern Medical Center, Dallas.

Although CombAT is only about halfway through its planned study period of 4 years, there are already numerous comparisons to the widely discussed Medical Therapy of Prostatic Symptoms (MTOPS) trial. That study compared the 5-alpha-reductase inhibitor finasteride (Proscar) with the alpha-blocker doxazosin (Cardura).

Major differences

Like the current CombAT data, MTOPS also showed the superiority of combination therapy for treating symptomatic BPH, but the differences between the two trials, Dr. Barkin noted, are significant. They include:

The result of those differences, Dr. Barkin said, is that CombAT patients are at a much higher risk of BPH progression.

Of the 4,844 men randomized to treatment in CombAT, 3,822 have completed follow-up through 24 months. All are 50 years or older with prostate volumes ≥30 cc. They were randomized to once-daily doses of dutasteride, 0.5 mg, tamsulosin, 0.4 mg, or the combination.

Symptoms were assessed every 3 months; peak urinary flow was checked every 6 months. The BPH Impact Index (BII) and question 8 of the IPSS, which asks how men would feel about having to take the drug or drugs they are on indefinitely, were asked at baseline and againt at 3-month intervals thereafter.

Investigators found that improvement in BII score from baseline was significantly greater (p<.01) with combination therapy versus dutasteride starting at 3 months, and versus tamsulosin beginning at 9 months.