Research Updates in Kidney and Urologic Health

Two-Drug Therapy Is Best for Symptomatic Prostate Enlargement

Combination Should Change Clinical Practice

Two drugs commonly used to treat benign prostatic hyperplasia (BPH) are more effective together than alone to prevent progression of this condition, according to the results of a multicenter National Institutes of Health clinical trial presented at the American Urological Association (AUA) meeting in Orlando in May 2002.

The Medical Therapy of Prostatic Symptoms (MTOPS) Trial found that the 5alpha-reductase inhibitor finasteride (Proscar) and alpha1-adrenoceptor antagonist doxazosin (Cardura) taken together reduced the risk of BPH progression by 67 percent compared with placebo. The risk of progression was reduced by 34 percent with finasteride alone and by 39 percent with doxazosin alone.

An estimated 9 million men have BPH symptoms, and each year about 400,000 have surgery to remove some of the enlarged gland that impairs the flow of urine through the urethra. Symptoms include urinary urgency, frequency, and nighttime urination.

"This is the kind of clear-cut result we all strive for when we launch a clinical trial," says Leroy M. Nyberg Jr., Ph.D., M.D., whose urology research program at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) funded the study. "The evidence supporting combination therapy in selected patients is so strong that I expect to see major changes in medical practice in the near future."

Physicians at 17 medical centers treated about 3,000 men age 50 and up for an average of 4.5 years. The men all had BPH and were evenly divided into four groups that took either 5 mg of finasteride, 4 mg or 8 mg of doxazosin, both drugs, or a placebo. The aim of the trial was to prevent BPH progression—defined primarily as a significant worsening of symptoms—and sequelae, including urinary tract infections, urinary retention, incontinence, or the need for invasive therapy such as surgery.

Compared with placebo, the risk of urinary retention was reduced by 79 percent with combination therapy, by 67 percent with finasteride, and by 31 percent with doxazosin (not significantly different from placebo). Furthermore, the risk of invasive therapy was reduced by 69 percent with the combination, by 64 percent with finasteride, and by 8 percent with doxazosin (not significantly different from placebo).

"Combination therapy not only provides better long-lasting symptom relief, but because finasteride reduces prostate size, patients have fewer episodes of urinary retention and invasive treatments," says MTOPS trial leader John McConnell, M.D., professor of urology and executive vice president of the University of Texas Southwestern Medical Center in Dallas. "In addition, the study clearly demonstrates which patients are at increased risk of progression and most likely to benefit from treatment."

When MTOPS began, doctors were prescribing each drug individually for BPH. But some doctors were concerned that while single-drug therapy provided partial relief, symptoms might worsen over time or the prostate might continue to enlarge, blocking the flow of urine and damaging the bladder and kidneys.

"In MTOPS, the rates of urinary tract infection and urinary incontinence were low in all drug treatment groups, and no patient in any group developed kidney problems from BPH. So we are very pleased," says Nyberg.

Researchers plan to publish the MTOPS data later in 2002. An abstract of Dr. McConnell's AUA presentation can be viewed at www.niddk.nih.gov/welcome/releases/05-28-02abstract.pdf on the NIDDK website.

The National Center on Minority Health and Health Disparities joined NIDDK in funding the study. Pfizer and Merck donated products.

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