Dutasteride/Tamsulosin May Be Helpful for Benign Prostatic Hyperplasia

Laurie Barclay
December 28, 2007 — In men with moderate to severe lower urinary tract symptoms (LUTS) and prostate enlargement (≥ 30 cc) from benign prostatic hyperplasia (BPH), combination therapy with tamsulosin and dutasteride provided significantly greater benefit vs tamsulosin or dutasteride monotherapy, according to the 2-year results from the Combination of Avodart and Tamsulosin (CombAT) study reported in the February issue of the Journal of Urology.
"The aim of the ongoing CombAT study is to investigate whether combination therapy with dutasteride and the alpha-blocker tamsulosin is more effective than either monotherapy alone for improving the symptoms and long-term clinical outcomes of AUR [acute urinary retention] and BPH related prostatic surgery in men with moderate to severe symptoms of BPH and a prostate volume of 30 cc or greater," write Claus G. Roehrborn, from the University of Texas Southwestern Medical Center in Dallas, Texas, and colleagues. "We report the results of analyses of the 2-year primary and secondary end points of LUTS, Qmax [peak urinary flow] and prostate volume, and further analyses of efficacy data as well as safety and tolerability outcomes."
In this ongoing, multicenter, double-blind, parallel group study, men 50 years or older with a clinical diagnosis of BPH and LUTS were randomized to receive 0.5 mg of dutasteride, 0.4 mg of tamsulosin, or the combination once daily for 4 years. Inclusion criteria were International Prostate Symptom Score (IPSS) of 12 points or greater, prostate volume 30 cc or greater, total serum prostate-specific antigen (PSA) of 1.5 ng/mL or greater to 10 ng/mL or less, and peak urinary flow greater than 5 to 15 mL per second or less with a minimum voided volume of 125 mL or greater.
LUTS were evaluated every 3 months, and peak urinary flow was evaluated every 6 months. The main outcome measure at 2 years was the change from baseline in IPSS.
Compared with monotherapy, combination therapy resulted in significantly greater improvements in LUTS vs dutasteride from month 3 and tamsulosin from month 9, and in BPH-related health status from months 3 and 12, respectively. From month 6, combination therapy was associated with a significantly greater improvement from baseline in peak urinary flow vs monotherapy dutasteride or tamsulosin monotherapies.
Compared with monotherapies, combination therapy was associated with a significant increase in drug-related adverse events. However, most of these did not necessitate stopping treatment.
"In men with moderate to severe lower urinary tract symptoms and prostate enlargement (≥ 30 cc) combination therapy provides a significantly greater degree of benefit than tamsulosin or dutasteride monotherapy," the study authors write.
A limitation of the CombAT study was the lack of a double placebo group, which could potentially exaggerate symptom response.
"Data from the remaining 2 years of the CombAT study will provide further information on the pattern of symptoms and long-term outcomes (AUR and the need for BPH related surgery) associated with combination therapy vs tamsulosin and dutasteride monotherapies," the study authors conclude.
GlaxoSmithKline supported this study. Some of the authors have disclosed various financial relationships with GlaxoSmithKline, Pfizer, Astellas, Merck, Indevus, Eli Lilly, and Bayer.
In an accompanying editorial comment, Steven A. Kaplan, from Weill Cornell Medical College of Cornell University in New York City, notes that one must be cautious not to overinterpret these findings. Nonetheless, he describes CombAT as "an important contribution to our evolving understanding of the management of LUTS."
"The 5-ARIs [5-alpha-reductase inhibitor] and specifically in this study dutasteride are widely accepted as the backbone of therapy because of their unparalleled [effect] on disease management and they are also highly effective for relieving symptoms in select patients," Dr. Kaplan writes. "The alpha-blockers probably do not work as effectively in large prostates as they do in smaller prostates. What remains indisputable is that prostate size and symptom type, ie storage vs voiding at baseline, will drive therapeutic choices and optimize outcomes."
J Urol. 2008;179:616-621. Published online December 19, 2007.