Complete Title: The influence of baseline parameters on changes in International Prostate Symptom Score (IPSS) after combined therapy with dutasteride plus tamsulosin or either monotherapy in men with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS): 4-year results CombAT study
OBJECTIVE: To examine, using post-hoc analysis, the influence of baseline parameters on changes in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax ) and IPSS quality of life (QoL) in men 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, randomised, double-blind, parallel-group study in 4844 men ≥50 years of age with a BPH clinical diagnosis by medical history and physical examination, an IPSS ≥12 points, prostate volume (PV) ≥30 cc, total serum PSA ≥1.5 ng/ml, and Qmax >5 ml/s and ≤ 15 ml/s with a minimum voided volume ≥125 ml. Eligible subjects were randomised to receive oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. Baseline parameter subgroups analysed were PV (30-< 40; 40-< 60; 60-< 80; ≥80 cc), PSA (1.5-< 2.5; 2.5-< 4; ≥4 ng/ml), age (median: < 66, ≥66 years), IPSS (median: <16, ≥16; IPSS thresholds: < 20, ≥20), IPSS QoL score (Q8) (median: < 4, ≥4), Qmax (median: < 10.4, ≥10.4 ml/s), BPH impact index (BII) (median: < 5, ≥5) and BMI (median: < 26.8, ≥26.8 kg/m2 ). Within each baseline parameter subgroup, changes in IPSS, Qmax and IPSS QoL Q8 from baseline were evaluated using a generalised linear model with effects for baseline IPSS, Qmax or IPSS QoL Q8 and treatment group at each post baseline assessment up to and including the month 48 visit using a last observation carried forward (LOCF) approach. The treatment comparisons of combination therapy vs. dutasteride and combination therapy vs. tamsulosin were performed from the general linear model with statistical significance defined as p≤ 0.01.
RESULTS: Combination therapy resulted in a significantly greater improvement from baseline IPSS at 48 months vs. tamsulosin monotherapy across all baseline subgroups. The benefit of combination therapy over dutasteride was confined to groups with lower baseline PV (< 60 cc) and PSA (< 4 ng/ml). In groups with baseline PV ≥60 cc and PSA ≥4 ng/ml, dutasteride and combination therapy show similar improvements in symptoms. Combination therapy resulted in significantly improved Qmax compared with tamsulosin but not dutasteride monotherapy. Qmax improvement appeared to increase with PV and PSA in combination therapy subjects. The proportion of subjects with an IPSS QoL of ≤ 2 (at least mostly satisfied) at 48 months was significantly higher with combination therapy than with dutasteride for subgroups with PV 40-60 cc and PSA < 4 ng/ml and compared with tamsulosin for all PSA subgroups and PV subgroups ≥40 cc.
CONCLUSION: CombAT data support the use of long-term combination therapy with dutasteride and tamsulosin in men considered at risk for progression of BPH, as determined by high PV (≥30 cc) and high PSA (≥1.5 ng/ml). Combination therapy, dutasteride monotherapy and tamsulosin monotherapy all improved Qmax , but to different extents (combination therapy > 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 parameters at 48 months. Compared with dutasteride, the superiority of combination therapy at 48 months was shown in men with PV< 60 cc or PSA < 4 ng/ml.
Written by:
Roehrborn CG, Barkin J, Tubaro A, Emberton M, Wilson TH, Brotherton BJ, Castro R. Are you the author?
Department of Urology, UT Southwestern Medical Center, Dallas, Texas, USA.
Reference: BJU Int. 2013 Oct 15. Epub ahead of print.
doi: 10.1111/bju.12500
PubMed Abstract
PMID: 24127818
