The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study.
BACKGROUND
Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement.


OBJECTIVE
To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression over 4 yr in men at increased risk of progression.


METHODS
The Combination of Avodart and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men > or =50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score > or =12, prostate volume > or =30 cm(3), prostate-specific antigen 1.5-10 ng/ml, and maximum urinary flow rate (Q(max)) >5 and < or =15 ml/s with minimum voided volume > or =125 ml.


METHODS
Oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both.


METHODS
The 4-yr primary end point was time to first AUR or BPH-related surgery. Secondary end points included BPH clinical progression, symptoms, Q(max), prostate volume, safety, and tolerability.


CONCLUSIONS
Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery. Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression. Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of an imbalance in the composite term of cardiac failure among the three study arms. The lack of placebo control is a study limitation.


CONCLUSIONS
The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement. CLINICALTRIALS.GOV IDENTIFIER: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).
Roehrborn
Claus G
CG
Department of Urology, UT Southwestern Medical Center, Dallas, Texas 75390-9110, USA. claus.roehrborn@utsouthwestern.edu
Siami
Paul
P
Barkin
Jack
J
Damião
Ronaldo
R
Major-Walker
Kim
K
Nandy
Indrani
I
Morrill
Betsy B
BB
Gagnier
R Paul
RP
Montorsi
Francesco
F
D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D001378:Azasteroids / Q000009:adverse effects / Q000627:therapeutic use*; D001938:Brazil; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068538:Dutasteride; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009656:North America; D016016:Proportional Hazards Models; D011470:Prostatic Hyperplasia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D000077409:Tamsulosin; D013997:Time Factors; D016896:Treatment Outcome; D016055:Urinary Retention / Q000188:drug therapy / Q000209:etiology; D013521:Urologic Surgical Procedures, Male
D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists; D001378:Azasteroids; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D000077409:Tamsulosin; D000068538:Dutasteride