To compare the efficacy and safety of silodosin and dutasteride combination with alfuzosin and dutasteride combination in patients of benign prostatic hyperplasia: a randomized, open label study
Keywords:Alfuzosin, BPH, Dutasteride, Silodosin
Background: BPH is a major cause of bothersome lower urinary tract symptoms (LUTS) and affects quality of life (QoL) which deteriorates if not taken care with the passage of time. The aim and objective of the study was to compare the efficacy and safety of combination of silodosin and dutasteride with the combination of alfuzosin and dutasteride in patients of BPH.
Methods: A randomized, open label, intention to treat study was carried out on newly diagnosed patients of BPH. Patients were randomly divided into two groups and followed up to 12 weeks. Group 1 of patients received a combination of silodosin 8 mg and dutasteride 0.5 mg (SD) (n=20) while the patients of group 2 received combination of alfuzosin 10 mg and dutasteride 0.5 mg (AD) (n=20). Primary endpoint was measured by changes in the mean baseline International prostate symptom score (I-PSS) and uroflowmetry and secondary outcome with changes observed on ultrasonography.
Results: IPSS and IPSS-QOL significantly improved in both the treatment groups (p <0.001) along with mean maximum flow rate (Qmax) and mean average flow rate (Qavg). Prostate volume and residual urine volume showed a significant improvement in both the treatment groups at 12 weeks. However, the intergroup differences in IPSS, uroflowmetry and USG parameters were not significant. Both treatments were well tolerated.Conclusions: The current study established that both the drug combinations i.e. silodosin and dutasteride (SD) and alfuzosin and dutasteride (AD) largely have a comparable effect on both the dynamic and static components of BPH. Further, both drug combinations appear to have a comparable safety profile.
Yoshida M, Kudoh J, Homma Y, Kawabe K. Safety and efficacy of silodosin for the treatment of benign prostatic hyperplasia. Clin Interventions Aging. 2011;6:161.
Yuan JQ, Mao C, Wong SY, Yang ZY, Fu XH, Dai XY, et al. Comparative effectiveness and safety of monodrug therapies for lower urinary tract symptoms associated with benign prostatic hyperplasia: a network meta-analysis. Med. 2015;94(27).
Park SG, Chung BH, Lee SW, Park JK, Park K, Cheon J, et al. Alpha-blocker treatment response in men with lower urinary tract symptoms based on sympathetic activity: prospective, multicenter, open-labeled, observational study. Inter Neurourol J. 2015;19(2):107.
Ding H, Du W, Hou ZZ, Wang HZ, Wang ZP. Silodosin is effective for treatment of LUTS in men with BPH: a systematic review. Asian J Androl. 2013;15(1):121.
Spatafora S, Casarico A, Fandella A, Galetti C, Hurle R, Mazzini E, et al. It BPH Guidelines Committee. Evidence-based guidelines for the treatment of lower urinary tract symptoms related to uncomplicated benign prostatic hyperplasia in Italy: updated summary from AURO. it. Therapeutic Adv Urol. 2012;4(6):279-301.
Yoo TK, Cho HJ. Benign prostatic hyperplasia: from bench to clinic. Korean J Urol. 2012;53(3):139-48.
Gokkaya CS, Aktas BK, Ozden C, Bulut S, Karabakan M, Erkmen AE, et al. Flurbiprofen alone and in combination with alfuzosin for the management of lower urinary tract symptoms. Central Euro J Urol. 2015;68(1):51.
Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, 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;179(2):616-21.
Ventimiglia B, Consoli S, Serrao M, Serrao A, Tsirgiotis A. Efficacy of dutasteride, alfuzosin or both on Quality of Life in patients with prostatic hyperplasia and BOO. A two-year spontaneous, observational, self-controlled study. Urol J. 2008;75(2):97-101.
Mehndiratta C, Gupta NP, Gopalakrishnan G, Cibber P, Sood R, Sarkar K. Effect of silodosin and dutasteride combination treatment in Indian patients of benign prostate hyperplasia with an enlarged prostate and co-morbid condition. Med Surg Urol. 2015;4(3):71.
Hagiwara K, Koie T, Iwamura H, Imai A, Hatakeyama S, Yoneyama T, et al. Efficacy and safety of silodosin and dutasteride combination therapy in acute urinary retention due to benign prostatic hyperplasia: a single-arm prospective study. BioMed Res Inter. 2016.
Arora S, Khajuria V, Gupta S, Tandon VR, Kohli K. Efficacy and tolerability of tamsulosin alone and in combination with dutasteride in patients of benign prostatic hyperplasia. JK Sci. 2012;14(3):134.
Roehrborn CG, Oyarzabal Perez I, Roos EP, Calomfirescu N, Brotherton B, Wang F, et al. Efficacy and safety of a fixed‐dose combination of dutasteride and tamsulosin treatment (D uodart®) compared with watchful waiting with initiation of tamsulosin therapy if symptoms do not improve, both provided with lifestyle advice, in the management of treatment‐naïve men with moderately symptomatic benign prostatic hyperplasia: 2‐year CONDUCT study results. BJU Inter. 2015;116(3):450-9.
Debruyne FM, Jardin A, Colloi D, Resel L, Witjes WP, Delauche-Cavallier MC, et al. Sustained-release alfuzosin, finasteride and the combination of both in the treatment of benign prostatic hyperplasia. Euro Urol. 1998;34(3):169-75.
Kawabe K. Silodosin Clinical Study Group. Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int. 2006;98:1019-24.
Marks LS, Gittelman MC, Hill LA, Volinn W, Hoel G. Rapid efficacy of the highly selective α1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies. J Urol. 2009;181(6):2634-40.
Manjunatha R, Pundarikaksha HP, Madhusudhana HR, Amarkumar J, Hanumantharaju BK. A randomized, comparative, open-label study of efficacy and tolerability of alfuzosin, tamsulosin and silodosin in benign prostatic hyperplasia. Ind J Pharmacol. 2016;48(2):134.
Nordling J. Efficacy and safety of two doses (10 and 15 mg) of alfuzosin or tamsulosin (0.4 mg) once daily for treating symptomatic benign prostatic hyperplasia. BJU Inter. 2005;95(7):1006-12.
Saad F, Nickel JC, Valiquette L, Casey R, Kuzmarov I, Elhilali M. Early symptom improvement of benign prostatic hyperplasia (BPH) treated with once daily alfuzosin. Can J Urol. 2005;12(4):2745-54.
Moon KH, Song PH, Yang DY, Park NC, Kim SW, Lee SW, et al. Efficacy and safety of the selective α1A-adrenoceptor blocker Silodosin for severe lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective, single-open-label, multicenter study in Korea. Korean J Urol. 2014;55(5):335-40.
Rossi M, Roumeguere T. Silodosin in the treatment of benign prostatic hyperplasia. Drug Des Dev Therapy. 2010;4:291.
van Kerrebroeck P, Jardin A, Van Cangh P, Laval KU, ALFORTI Study Group. Long-term safety and efficacy of a once-daily formulation of alfuzosin 10 mg in patients with symptomatic benign prostatic hyperplasia: open-label extension study. Euro Urol. 2002;41(1):54-61.
Chapple CR, Wyndaele JJ, Nordling J, Boeminghaus F, Ypma AF. European Tamsulosin Study Group, et al. Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. A meta-analysis of two randomized, placebo-controlled, multicentre studies in patients with benign prostatic obstruction (symptomatic BPH). Eur Urol. 1996; 29(2):155-67.
Matsukawa Y, Gotoh M, Komatsu T, Funahashi Y, Sassa N, Hattori R. Efficacy of silodosin for relieving benign prostatic obstruction: prospective pressure flow study. J Urol. 2009;182(6):2831-5.
Yanardag H, Goktas S, Kibar Y, Kilic S, Erduran D. Intermittent tamsulosin therapy in men with lower urinary tract symptoms. J Urol. 2005;173(1):155-7.
Salinas J. Clinical and urodynamic results of alpha-blocker drug treatment in patients with lower urinary tract symptoms and benign prostatic hyperplasia. Arch Esp Urol. 2015;68(2):161-71.
Zhang LT, Lee SW, Park K, Chung WS, Kim SW, Hyun JS, et al. Multicenter, prospective, comparative cohort study evaluating the efficacy and safety of alfuzosin 10 mg with regard to blood pressure in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia with or without antihypertensive medications. Clin Inter Aging. 2015;10:277.
Barendrecht MM, Koopmans RP, La Rosette JJ, Michel MC. Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: the cardiovascular system. BJU Inter. 2005;95:19-28.