silodosin and Prostatic-Neoplasms

To compare the effects of naftopidil and silodosin administration on the quality of life of patients with prostate cancer who underwent low-dose-rate brachytherapy.. In total, 141 men diagnosed with localized prostate cancer who were treated with low-dose-rate brachytherapy were enrolled. Patients were randomized (1:1) to the naftopidil (75 mg/day, n = 63) or silodosin group (8 mg/day, n = 64). Naftopidil and silodosin were administered 1 day after low-dose-rate brachytherapy, and were continued for at least 3 months. Using the University of California at Los Angeles Prostate Cancer Index and Sexual Health Inventory for Men scores, the mean changes and rates of deterioration from baseline were compared. The deterioration rates in the quality of life of patients at 1 and 3 months after low-dose-rate brachytherapy were evaluated based on the minimal important difference.. The rates of deterioration from baseline to 1 and 3 months after low-dose-rate brachytherapy were not significantly different between the two groups in terms of urinary function, urinary bother, bowel bother, sexual function or Sexual Health Inventory for Men scores. In contrast, there were significant differences in bowel function (naftopidil 1 month, 52%; 3 months, 52%; silodosin 1 month, 28%; 3 months, 34%; 1 month, P < 0.01; 3 months, P = 0.048) and sexual bother (naftopidil 3 months, 11%; silodosin 3 months, 29%; P = 0.01).. Naftopidil and silodosin provide different disease-specific quality of life outcomes in patients undergoing, especially in terms of bowel function and sexual bother. These findings can help in the selection of α-1 adrenoceptor antagonists after low-dose-rate brachytherapy.

Topics: Brachytherapy; Humans; Indoles; Male; Naphthalenes; Piperazines; Prostatic Neoplasms; Quality of Life

The purpose of the study is to investigate the efficacy of an alpha-1 adrenergic receptor antagonist (silodosin) for the treatment of lower urinary tract symptoms (LUTS) associated with interstitial (125)I implantation for prostate cancer.. This randomized single-center study involved 105 patients (53 with and 52 without silodosin). Silodosin was postoperatively administered, daily, for 6 months (8 mg/day). Urinary symptoms and pressure flow were evaluated preoperatively and postoperatively at 1, 3, 6, and 12 months.. At 12 months, interstitial (125)I implantation had induced a significant decrease in prostate volume (28.3 ± 11.1-20.5 ± 8.1 g in the silodosin group and 26.1 ± 9.7-17.7 ± 4.9 g in the controls) and the prostate-specific antigen level (7.1 ± 3.6-1.4 ± 1.7 ng/mL in the silodosin group and 8.1 ± 4.3-1.3 ± 1.2 ng/mL in the controls). Significant improvements in the international prostate symptom voiding subscores at 6 months and quality of life at 3 months were observed in those receiving silodosin. The pressure flow studies demonstrated that silodosin had significantly enlarged the bladder capacity when the first non-voiding contraction was seen at 3 and 12 months (3M: 127.1 ± 74.8 vs. 118.2 ± 83.9 mL, p = 0.001; 12M: 123.7 ± 79.3 vs. 100.3 ± 73.4 mL, p = 0.01); however, there were no improvements in the bladder outlet obstruction index (BOOI) or urinary flow.. Silodosin temporarily improved LUTS, but did not improve the BOOI after (125)I implantation in the prostate.

Topics: Adrenergic alpha-1 Receptor Antagonists; Aged; Brachytherapy; Humans; Indoles; Lower Urinary Tract Symptoms; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Treatment Outcome; Urinary Bladder Neck Obstruction; Urodynamics

To evaluate the effect of two different alpha-1 adrenoceptor antagonists on lower urinary tract symptoms in patients who underwent LDR-brachytherapy.. A total of 141 patients who had been clinically diagnosed with localized prostate cancer and underwent LDR-brachytherapy were enrolled. Patients were randomized and allocated to two groups (silodosin 8 mg vs. naftopidil 75 mg). The primary endpoint was a change in the international prostate symptom score (IPSS) at 3 months after seed implantation. Secondary endpoints included the recovery rate of IPSS at 12 months after seed implantation, the change in IPSS and overactive bladder symptom score, uroflowmetric parameters, and frequency volume chart (FVC). To determine independent variables that can predict IPSS recovery, logistic regression analysis was carried out.. The mean change in the IPSS at 3 months after seed implantation in both groups was ⊿10.6 (naftopidil) and ⊿10.4 (silodosin), respectively. There was not a significant difference between the two groups (p=0.728). An increase in urinary frequency and a decrease in total urinated volume and mean voided volume were observed in FVC for 12 months after seed implantation. Multivariate analysis revealed that the urethral dose (UD30) was an independent predictive parameter of IPSS recovery. Patients with UD30 < 200Gy showed a higher recovery rate of IPSS at 12 months after seed implantation.. There was no significant difference of serial change in IPSS between silodosin and naftopidil during the first year after seed implantation. A lower dose on the urethra was an independent predictor of IPSS recovery at 12 months after seed implantation.

Topics: Adrenergic alpha-1 Receptor Antagonists; Aged; Aged, 80 and over; Brachytherapy; Humans; Indoles; Male; Middle Aged; Naphthalenes; Piperazines; Prostatic Neoplasms; Urinary Bladder, Overactive

To compare the efficacy of three α(1A)/α(1D)-adrenoceptor (AR) antagonists--naftopidil, tamsulosin, and silodosin--that have differing affinities for the α(1)-AR subtypes in treating urinary morbidities in Japanese men with (125)I prostate implantation (PI) for prostate cancer.. This single-institution prospective randomized controlled trial compared naftopidil, tamsulosin, and silodosin in patients undergoing PI. Patients were randomized and received either naftopidil, tamsulosin, or silodosin. Treatment began 1 day after PI and continued for 1 year. The primary efficacy variables were the changes in total International Prostate Symptom Score (IPSS) and postvoid residual urine (PVR). The secondary efficacy variables were changes in IPSS storage score and IPSS voiding score from baseline to set points during the study (1, 3, 6, and 12 months).. Two hundred twelve patients were evaluated in this study between June 2006 and February 2009: 71, 70, and 71 patients in the naftopidil, tamsulosin, and silodosin groups, respectively. With respect to the primary efficacy variables, the mean changes in the total IPSS at 1 month after PI in the naftopidil, tamsulosin, and silodosin groups were +10.3, +8.9, and +7.5, respectively. There were significantly greater decreases with silodosin than naftopidil at 1 month in the total IPSS. The mean changes in the PVR at 6 months were +14.6, +23.7, and +5.7 mL in the naftopidil, tamsulosin, and silodosin groups, respectively; silodosin showed a significant improvement in the PVR at 6 months vs. tamsulosin. With respect to the secondary efficacy variables, the mean changes in the IPSS voiding score at 1 month in the naftopidil, tamsulosin, and silodosin groups were +6.5, +5.6, and +4.5, respectively; silodosin showed a significant improvement in the IPSS voiding score at 1 month vs. naftopidil.. Silodosin has a greater impact on improving PI-induced lower urinary tract symptoms than the other two agents.

Topics: Adrenergic alpha-1 Receptor Antagonists; Aged; Analysis of Variance; Brachytherapy; Humans; Indoles; Iodine Radioisotopes; Lower Urinary Tract Symptoms; Male; Naphthalenes; Piperazines; Prospective Studies; Prostatic Hyperplasia; Prostatic Neoplasms; Quality of Life; Radiotherapy Dosage; Sulfonamides; Tamsulosin

Topics: Brachytherapy; Humans; Indoles; Male; Naphthalenes; Piperazines; Prostatic Neoplasms; Quality of Life

Biological significance of ELK1, a transcriptional factor whose phosphorylation is necessary for c-fos proto-oncogene activation, in prostate cancer remains far from fully understood. In this study, we aim to investigate the role of ELK1 in tumor growth as well as the efficacy of a selective α1A-adrenergic blocker, silodosin, in ELK1 activity in prostate cancer cells.. We first immunohistochemically determined the levels of phospho-ELK1 (p-ELK1) expression in radical prostatectomy specimens. We then assessed the effects of ELK1 knockdown via short hairpin RNA and silodosin on cell proliferation, migration, and invasion in prostate cancer lines.. The levels of p-ELK1 expression were significantly higher in carcinoma than in benign (P < 0.001) or high-grade prostatic intraepithelial neoplasia (HGPIN) (P = 0.002) as well as in HGPIN than in benign (P < 0.001). Kaplan-Meier and log-rank tests revealed that moderate-strong positivity of p-ELK1 in carcinomas tended to correlate with biochemical recurrence after radical prostatectomy (P = 0.098). In PC3 and DU145 expressing ELK1 (mRNA/protein) but no androgen receptor (AR), ELK1 silencing resulted in considerable decreases in the expression of c-fos as well as in cell migration/invasion and matrix metalloproteinase-2 expression, but not in cell viability. Silodosin treatment reduced the expression/activity of ELK1 in these cells as well as the viability of AR-positive LNCaP and C4-2 cells and the migration of both AR-positive and AR-negative cells, but not the viability of AR-negative or ELK1-negative cells. Interestingly, silodosin significantly increased sensitivity to gemcitabine, but not to cisplatin or docetaxel, even in AR-negative cells.. ELK1 is likely to be activated in prostate cancer cells and promote tumor progression. Furthermore, silodosin that inactivates ELK1 in prostate cancer cells not only inhibits their growth but also enhances the cytotoxic activity of gemcitabine. Thus, ELK1 inhibition has the potential of being a therapeutic approach for prostate cancer.

Topics: Adrenergic alpha-1 Receptor Antagonists; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Proliferation; Deoxycytidine; Drug Interactions; ets-Domain Protein Elk-1; Gemcitabine; Gene Silencing; Humans; Indoles; Male; Neoplasm Invasiveness; Phosphorylation; Prostate; Prostatectomy; Prostatic Neoplasms; Proto-Oncogene Mas; Receptors, Androgen

Some α1 -adrenoceptor antagonists possess anti-cancer actions that are independent of α1 -adrenoceptors and the aim of these studies was to assess the relative cytotoxic potencies of α1 -adrenoceptor antagonists and the mechanisms involved in these actions.. PC-3 and LNCap human prostate cancer cells were exposed to α1 -adrenoceptor antagonists (0.01-100 μM) and cell survival assessed after 24-72 hr. The levels of apoptosis, autophagy and stress related proteins were also determined.. The relative cytotoxic potency order was prazosin = doxazosin > terazosin = silodosin = alfuzosin > tamsulosin on both cell types, but LNCaP cells were significantly more sensitive to these effects than PC-3 cells. Prazosin and doxazosin increased levels of apoptotsis and autophagy in both cell lines, and activated EphA2 receptors in PC-3 cells. Autophagy contributed to survival of LNCaP, but promoted cell death in PC-3 cells. Treatment with prazosin (30 μM) altered the expression of several cell stress-related proteins: elevating phospho-p38α and reducing S6 kinase in both cell lines. Surprisingly some proteins were differentially affected in the two prostate cancer cell lines: Akt and p27 increasing and HIF-1α decreasing in LNCap cells but not PC-3, while ADAMTS1 was increased in PC-3 cells only.. Prazosin and doxazosin demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. The mechanisms involved included changes in a number of proliferation and apoptosis regulatory proteins. The role of autophagy depended on the cell type, but contributed to cell death in PC3 cells.

Topics: Adrenergic alpha-1 Receptor Antagonists; Antineoplastic Agents; Apoptosis; Autophagy; Cell Death; Cell Line, Tumor; Cell Survival; Doxazosin; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Indoles; Male; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Prazosin; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Quinazolines; Signal Transduction; Sulfonamides; Tamsulosin