Elsevier

European Urology

Volume 57, Issue 1, January 2010, Pages 123-131
European Urology

Benign Prostatic Hyperplasia
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

https://doi.org/10.1016/j.eururo.2009.09.035Get rights and content

Abstract

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.

Design, setting, and participants

The Combination of Avodart® and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men ≥50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score ≥12, prostate volume ≥30 cm3, prostate-specific antigen 1.5–10 ng/ml, and maximum urinary flow rate (Qmax) >5 and ≤15 ml/s with minimum voided volume ≥125 ml.

Intervention

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

Measurements

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

Results and limitations

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).

Introduction

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) is a progressive disease [1], [2], [3], [4], [5]. Medical management of LUTS due to BPH with α-blockers and/or 5α-reductase inhibitors (5-ARIs) is the first-line treatment; these two drug classes have shown different abilities to influence likelihood of progression [6], [7], [8]. The 4-yr Combination of Avodart® and Tamsulosin (CombAT) study was initiated to investigate whether combination therapy with dutasteride and tamsulosin was more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression in men with moderate-to-severe LUTS due to BPH who were predicted to be at increased risk of progression by virtue of having a prostate volume ≥30 cm3and prostate-specific antigen (PSA) ≥1.5 ng/ml [9].

In this paper, we report the 4-yr results of CombAT relating to the risks of AUR, BPH-related surgery, overall clinical progression, and symptom progression, as well as symptom improvement, maximum urinary flow rate (Qmax) improvement and prostate volume and serum PSA changes.

Section snippets

Study design

The design of the multinational, multicenter, randomised, double-blind, parallel-group CombAT study has been previously reported [9], [10], [11]. Briefly, eligible subjects were randomised to receive one of the following treatments orally once daily for a period of 4 yr: dutasteride 0.5 mg and tamsulosin 0.4 mg, dutasteride 0.5 mg and tamsulosin-matched placebo, or dutasteride-matched placebo and tamsulosin 0.4 mg. Details of AUR and BPH-related prostatic surgery episodes were recorded at every

Subject disposition and demographics

Of the 4844 men randomised to treatment, 3195 (66%) completed the month 48 visit (Fig. 1). A numerically higher rate of discontinuation was observed in the tamsulosin group (39%) compared with the combination (31%) or dutasteride (33%) groups, and more patients in the tamsulosin group withdrew due to lack of efficacy. Table 2 summarises the patient demographics and baseline characteristics: These were similar across treatment groups.

Primary end point: acute urinary retention or benign prostatic hyperplasia-related prostatic surgery

The time to first AUR or BPH-related surgery was significantly

Discussion

In men with moderate-to-severe LUTS due to BPH, dutasteride and tamsulosin combination therapy significantly reduced the relative risk of AUR or BPH-related surgery over 4 yr by 66% compared with tamsulosin monotherapy. No significant difference was observed between combination therapy and dutasteride, which is concordant with other data [7]. Furthermore, combination therapy significantly reduced the relative risk of BPH clinical progression and symptom deterioration of IPSS ≥4 points (the most

Conclusions

The 4-yr data from the CombAT study 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 at increased risk of progression. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of the imbalance in cardiac failure.

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