Benign Prostatic HyperplasiaThe 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
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.
References (14)
- et al.
Benign prostatic hyperplasia: a progressive disease of aging men
Urology
(2003) - et al.
Natural history of benign prostatic hyperplasia
Urology
(2001) - et al.
Serum prostate-specific antigen and prostate volume predict long-term changes in symptoms and flow rate: results of a four-year, randomized trial comparing finasteride versus placebo
Urology
(1999) - et al.
Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia
Urology
(1999) - et al.
The long-term outcome of medical therapy for BPH
Eur Urol
(2007) - et al.
Combination therapy with dutasteride and tamsulosin in men with moderate-to-severe benign prostatic hyperplasia and prostate enlargement: the CombAT (Combination of Avodart® and Tamsulosin) trial rationale and study design
Contemp Clin Trials
(2007) - et al.
The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study
J Urol
(2008)
Cited by (599)
The human microbiome and benign prostatic hyperplasia: Current understandings and clinical implications
2024, Microbiological ResearchIs there a best timing for benign prostatic hyperplasia surgery?
2024, French Journal of UrologyDecoding the complexity of benign prostatic hyperplasia therapies in the PARTEM trial—authors’ reply
2024, The Lancet Regional Health - EuropeDecoding the complexity of benign prostatic hyperplasia therapies in the PARTEM trial
2024, The Lancet Regional Health - Europe