ROLE OF SILODOSIN IN PATIENTS WITH LOWER URINARY TRACT SYMPTOMS ASSOCIATED WITH BENIGN PROSTATIC ENLARGEMENT NON-RESPONDERS TO MEDICAL TREATMENT WITH TAMSULOSIN
The aim of our study was to evaluate the effect of silodosin in patients with lower urinary tract symptoms associated with benign prostatic enlargement (BPE/LUTS) non-responders to medical terapy with tamsulosin.
Materials and Methods
Patients who were taking tamsulosin 0,4 mg once daily for BPE/LUTS at last 12 months who visited the our centers from May 2015 to July 2016 were enrolled. The inclusion criteria were as follows: International Prostate Symptoms Score (IPSS) ≥ 8 points; Bother score (BS) ≥ 3 points; prostate volume measured by ultrasonographic method ≤ 40 mL; maximal urinary flow rate (Qmax) < 15 mL/s and post-voiding residual (PVR) ≤ 150 ml. Patients enrolled stopped tamsulosin and began terapy with silodosin 8 mg once daily. The symptom scores and uroflowmetry with PVR evaluation were measured 8 weeks after silodosin administration. Furthermore we investigated adverse drug reactions throughout the study period. The primary end-point of evaluation for efficacy was the change in IPSS and BS from the beginning of silodosin terapy; secondary end-points were changes in objective parameters (Qmax, PVR). Changes from baseline after the initiation of administration were evaluated by t-test. Values are the mean ± standard deviation, and findings of P < 0.05 were considered significant. Statistical analyses were performed with SAS 9.1.3 for Microsoft Windows (SAS Institute Inc, NC, USA).
One hundred-nine patients were enrolled in the study. Change in IPSS total score after administration of silodosin was -2.8 ± 3.7 (18.6 ± 5.1 versus 15,3 ± 1.9) (p < 0,05). Similar changes were observed in subscores of IPSS, that is, voiding symptoms, storage symptoms and post-micturition symptoms. The results about BS were similar to those for IPSS (4.2 ± 1.2 versus 3.7 ± 1.3) (p < 0,05). Qmax (10.9 ± 2.0 versus 11.9 ± 1.8) and PVR (103.4 ± 34.3 versus 99.6 ± 23.6) were not significantly improved (p > 0,05). Adverse drug reactions were observed in 19 of 109 patients (17.4%) after administration of silodosin. The most frequently observed adverse drug reaction to silodosin was ejaculatory disorder in 7 patients (7.2%).
α1-Blockers (ABs) are frequently prescribed as first-line therapy for the treatment of moderate to severe LUTS/BPE. To date, six ABs have been approved for the treatment of LUTS/BPE: terazosin, doxazosin, tamsulosin, naftopidil (not available in western), alfuzosin (not available in japan) and silodosin. All of them have been reported to significantly improve voiding and storage LUTS(1). Efficacy of ABs was similar. However, their efficacy differs among individuals. Therefore, in daily clinical practice, we switch agents when one is not effective(2). Compared with non-selective ABs, drugs with a high selectivity for α1A-adrenoreceptors (α1A-ARs) may be more prostate-specific and maintain a therapeutic response in the treatment of symptomatic BPE with less systemic adverse effects. Silodosin was demonstrated to have a higher selectivity for the α1A-AR subtype than other ABs(3). A recent meta-analysis demonstrated, for the first time, that ABs can generate significant urodynamic outcomes in patients treated for LUTS/BPE. Interestingly, the meta-analysis showed a statistically significant benefit in favor of AB drugs in terms of bladder outfflow obstruction index (BOOI) and detrusor pressure at maximum flow (PdetQmax). Although no direct comparisons have ever been performed among different ABs, the highest levels of BOOI improvement were reported in the studies on silodosin, which differs from other ABs in its high pharmacologic selectivity for the α1A receptor subtype. However, if and how urodynamic efficacy depends on pharmacologic selectivity is still to be verified(1). Miyakita et al compared the efficacy and safety of silodosin and tamsulosin in LUTS patients with BPE by a randomized crossover method. In this study, silodosin significantly improved storage and post-micturition symptoms in addition to voiding symptoms in both the first and crossover treatment periods. Furthermore, it significantly improved nocturia, which among LUTS markedly affects quality of life, regardless of the period of administration(4). Similar effects we observed in our study in patients with BPE/LUTS non-responders to medical treatment (tamsulosin). IPSS and BS improved while we did not observe changes of Qmax and PVR. Statistical power of our study was weakened. Therefore, further prospective studies should be conducted with greater number of patients. However we think that these preliminary data which is contributed to the literature will be helpful as guiding tools for future investigations.
In our study we showed, for the first time, that silodosin improve symtomps score and quality of life test (IPSS and BS) in patients with LUTS/BPE non-responders to terapy with tamsulosin.
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(2) Araki T, Monden K, Araki M. Comparison of 7 α1-adrenoceptor Antagonists in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia: A Short-term Crossover Study. Acta medica Okayama 2013;67(4):245-51
(3) 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):121-8
(4) Miyakita H, Yokoyama E, Onodera Y, Utsunomiya T, Tokunaga M, Tojo T, Fujii N, Yanada S. Short-term effects of crossover treatment with silodosin and tamsulosin hydrochloride for Lower Urinary Tract Symptoms associated with Benign Prostatic Hyperplasia. Int J Urol 2010;17(10):869-75Argomenti: ipertrofia prostatica