Efficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH

Abstract

Although ethnicity-based differences in prostate size and physiology have been reported, results of benign prostatic hyperplasia (BPH) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian populations. This post hoc analysis investigated whether an Asian subpopulation of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study population. In this doubleblind, randomized, parallel-group trial, 325 Asian men were assigned to treatment with 0.5 mg dutasteride once daily, 0.4 mg tamsulosin once daily or the combination. Decrease in international prostate symptom score (IPSS) at month 24 from baseline (the primary endpoint) was significantly greater with combination treatment compared with tamsulosin (Po0.05), and numerically, but not statistically significantly, greater compared with dutasteride. Mean IPSS was reduced from baseline by 7.5 (±0.84) in the combination group, by 6.3 (±0.86) in the dutasteride group and by 4.5 (±0.78) in the tamsulosin group, resulting in respective mean IPSS at months 24 of 11.4 (±0.60), 12.7 (±0.70) and 14.3 ( ± 0.74). The adverse event profile was similar to that observed in the overall CombAT population, and drug-related adverse events were more common with combination therapy (26%) than with tamsulosin (15%) or dutasteride (9%). No unexpected adverse events emerged. In conclusion, in Asian men with moderate-to-severe lower urinary tract symptoms and an enlarged prostate, combination therapy achieved significantly greater improvements from baseline BPH symptoms, flow rate, quality of life, reduced prostate volume and improved treatment satisfaction compared with tamsulosin monotherapy.

JUA clinical guidelines for benign prostatic hyperplasia

“…The cumulative rates of progression were 17% in the placebo group, 10% in the doxazosin and finasteride groups, and 5% in the combination therapy group. We can also expect an additive effect from combination therapy in Japanese patients, from similar results in the Asian sub‐population as in all patients in the CombAT study, 324 and from a similar (additive) effect for dutasteride, regardless of whether or not the patients had previously been administered tamsulosin, in a sub‐analysis of a Japanese Phase III trial 100 . We await the results of future trials conducted with Japanese patients, including examinations of cost effectiveness.…”

Outline of JUA clinical guidelines for benign prostatic hyperplasia

“…117 The risk of clinical progression during 4.5 years (5%) was significantly less in the combination therapy group. A similar additive effect of combination therapy is suggested in Japanese men, 25,118 although trials on its efficacy and cost effectiveness in Japanese men are awaited.…”

Benign prostatic hyperplasia and prostate-specific antigen

“…After 24 months, the decrease of TPV was 30.5% (combination therapy), or 28.6% (dutasteride). These studies conclude that the enlarged prostate and elevated PSA are good predictors of complications such as acute urinary retention and need for surgery, while the severity of symptoms and lower flow often behave paradoxically [56][57][58] . …”