Prostate-specific antigen (178-187)

Objective: To examine, using post hoc analysis, the influence of baseline variables on changes in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax ) and IPSS quality of life (QoL) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with either the α-blocker tamsulosin or the dual 5-alpha reductase inhibitor dutasteride, alone or in combination, as part of the 4-year Combination of Avodart and Tamsulosin (CombAT) study. Patients and methods: CombAT was a 4-year, multicentre, randomized, double-blind, parallel-group study in 4844 men ≥50 years of age with a clinical diagnosis of BPH by medical history and physical examination, an IPSS ≥12 points, prostate volume (PV) ≥30 mL, total serum PSA level ≥1.5 ng/mL, and Qmax >5 mL/s and ≤15 mL/s with a minimum voided volume ≥125 mL. Eligible subjects were randomized to receive oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. Baseline variable subgroups analysed were as follows: PV (30 to dutasteride >> tamsulosin), suggesting that dutasteride contributes most to the Qmax benefit in combination therapy. Combination therapy provided consistent improvement over tamsulosin in LUTS across all analysed baseline variables at 48 months. Compared with dutasteride, the superiority of combination therapy at 48 months was shown in patients with PV <60 mL or PSA <4 ng/mL.

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 > 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. 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, Q(max), 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).

Objective: · To investigate the influence of baseline variables on the 4-year incidence of acute urinary retention (AUR), benign prostatic hyperplasia (BPH)-related surgery and overall clinical progression in men treated with tamsulosin, dutasteride, or a combination of both. Patients and methods: · The 4-year Combination of Avodart® and Tamsulosin (CombAT) study was a multicenter, randomized, double-blind, parallel-group study of clinical outcomes in men aged ≥ 50 years with symptomatic (International Prostate Symptom Score [IPSS]≥ 12) BPH, with prostate-specific antigen (PSA) levels of ≥ 1.5 ng/mL and ≤ 10 ng/mL, and a prostate volume (PV) of ≥ 30 mL. · Eligible patients received tamsulosin 0.4 mg, dutasteride 0.5 mg, or a combination of both. · The primary endpoint was time to first AUR or BPH-related surgery. Secondary endpoints included clinical progression of BPH and symptoms. Posthoc analyses of the influence of baseline variables (including age, IPSS health-related quality of life [HRQL], PV, PSA, IPSS, peak urinary flow rate [Q(max) ] and body-mass index [BMI]) on the incidence of AUR or BPH-related surgery, clinical progression of BPH, and symptoms were performed. Results: · There were 4844 men in the intent-to-treat population. Overall baseline characteristics were similar across all patient groups. · Regardless of baseline subgroup, the incidence of AUR or BPH-related surgery was higher in men treated with tamsulosin than in those treated with dutasteride or combined therapy. · Combined therapy was statistically better than tamsulosin in reducing the risk of AUR or BPH-related surgery in subgroups of baseline PV > 42.0 mL, in all subgroups of baseline PSA level, and all other baseline subgroups (P ≤ 0.001). · Across treatment groups, the incidence of clinical progression was highest in men with a baseline IPSS of < 20 or IPSS HRQL score of < 4. The incidence of clinical progression was also higher in men receiving tamsulosin than dutasteride or combined therapy in all baseline subgroups, except for men with a baseline PV of < 40 mL. Combined therapy reduced the relative risk (RR) of clinical progression compared with tamsulosin across all baseline subgroups and compared with dutasteride across most baseline subgroups. · Symptom deterioration was the most common progression event in each treatment group regardless of baseline subgroup, except in those men with an IPSS of ≥ 20 at baseline. Combined therapy reduced the RR of symptom deterioration compared with tamsulosin across all but one baseline subgroup (the reduction was not significant for men with a baseline PV of < 40 mL) and compared with dutasteride in most subgroups. Conclusions: · Men with a baseline PV of ≥ 40 mL and any baseline PSA level of ≥1.5 ng/mL had greater reductions in the RR of AUR or BPH-related surgery and greater reductions in the RR of clinical progression and symptom deterioration on combined therapy or dutasteride monotherapy than on tamsulosin monotherapy. · These analyses support the long-term use of combined therapy with dutasteride plus tamsulosin in men with moderate-to-severe BPH symptoms and a slightly enlarged prostate.