==PROSTATE ENLARGMENT AND URINATION== 1 AUTHOR Chapple CR AUTHOR Wyndaele JJ AUTHOR Nordling J AUTHOR Boeminghaus F AUTHOR Ypma AF AUTHOR Abrams P TITLE 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). European Tamsulosin Study Group. SOURCE Eur Urol; VOL 29, ISS 2, 1996, P155-67 ABSTRACT OBJECTIVE: This meta-analysis of two European studies evaluated the efficacy and safety of modified-release tamsulosin 0.4 mg once daily compared with placebo in patients with benign prostatic enlargement, lower urinary tract symptoms and prostatic obstruction (symptomatic BPH). METHODS: Patients entered a 2-week placebo run-in period, followed by randomization to treatment with tamsulosin (382 patients) or placebo (193 patients) once daily for 12 weeks. RESULTS: Maximum urinary flow rate improved to a greater extent in the tamsulosin group (1.6 ml/s, 16%) than the placebo group (0.6 ml/s, 6%) (p = 0.002). Total Boyarsky symptom score also improved to a greater extent in the tamsulosin group (3.3 points, 35.1% reduction) than the placebo group (2.4 points, 25.5% reduction) (p = 0.002). Significantly more tamsulosin patients (66%) than placebo patients (49%) had a > or = 25% decrease in total symptom score at endpoint (p < 0.001). Twelve weeks of treatment with tamsulosin also produced significant improvements in average urinary flow rate (p = 0.005) and voiding or "obstructive" (p = 0.008) and storage or "irritative' (p = 0.017) symptom scores. The incidence of drug-related adverse events was comparable for the tamsulosin and placebo groups (13 and 12% respectively, p = 0.802). The same applies to the incidence of adverse events commonly attributed to alpha 1-adrenoceptor antagonists, such as dizziness, headache, postural hypotension, syncope, asthenia, somnolence and rhinitis. There were no clinically significant changes in blood pressure or pulse rate in tamsulosin patients compared with placebo patients both in hypertensive and normotensive BPH patients. CONCLUSION: Tamsulosin 0.4 mg once daily is safe, well-tolerated and improves both the symptoms and urinary flow rate in patients with benign prostatic obstruction (symptomatic BPH). 2 AUTHOR Schulman CC AUTHOR Cortvriend J AUTHOR Jonas U AUTHOR Lock TM AUTHOR Vaage S AUTHOR Speakman MJ TITLE Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. Analysis of a multinational, multicentre, open-label study assessing the long-term efficacy and safety in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin Study Group. SOURCE Eur Urol; VOL 29, ISS 2, 1996, P145-54 ABSTRACT OBJECTIVE: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with benign prostatic enlargement, lower urinary tract symptoms and benign prostatic obstruction (symptomatic BPH) for up to 60 weeks. METHODS: Patients were enrolled from two European, 12-week, placebo-controlled trials. This 60-week interim analysis includes the patients (n = 244) randomized to tamsulosin in the two placebo-controlled trials. RESULTS: The significant improvements in the primary efficacy parameters, maximum urinary flow rate (Qmax) and total Boyarsky symptom score, that were observed during the placebo-controlled trials, were sustained throughout the long-term extension study. Mean Qmax improved from baseline (before initiation of tamsulosin) to endpoint by 13.7% (p < 0.001) and remained between 11.5 and 12 ml/s during the entire follow-up period. Total Boyarsky symptom score improved by 36.2% from baseline to endpoint (p < 0.001). Similarly, the percentage of treatment responders, defined as an increase in Qmax of > or = 30% or a decrease in total symptom score of > or = 25%, remained constant throughout the 60-week period. At endpoint, 69% of patients demonstrated this clinically significant total Boyarsky symptom score response. During the 60-week study period, 51 patients (21%) experienced an adverse event considered to be possibly or probably related to study medication, the most common of which were dizziness and abnormal ejaculation, both occurring in 5% of patients. There were no clinically significant changes in blood pressure or pulse rate during the study. CONCLUSION: Long-term tamsulosin therapy is safe, well tolerated and improvements in urinary flow and symptoms are maintained for at least 60 weeks of treatment. 1 AUTHOR Pytel' IuA AUTHOR Vinarov AZ TITLE [Proscar (finasteride, MSD) in the treatment of patients with prostatic hyperplasia] SOURCE Urol Nefrol (Mosk), ISS 4, 1996, P25-7 ABSTRACT The drug proskar (finasteride) belongs to 5 alpha-reductase blockers breaking the steps of prostatic adenoma pathogenesis. Proskar (Merck and Co. Inc., USA) was given to 38 patients with prostatic adenoma stage I and II (residual urine < 50 ml) admitted to urological clinic of the Moscow Medical Academy in 1993-1995. Daily dose was 5 mg. In patients with associated inflammation it was treated prior to proskar administration. To reject carcinoma, patients with elevated levels of prostatic specific antigen (< 4 ng/ml) were subjected to polyfocal biopsy of the gland. In any case, these patients received antiandrogens flutamide or androkur. Subjective response was achieved in 33 of 38 patients (86.8%). Better urination was reported in 29 patients (76.3%). Abdominal and transrectal ultrasonic scanning registered a decrease in the size of the prostate in 25 (65.8%) patients. Proskar was well tolerated, sexual disturbances occurred only in 2 patients. Proskar is effective in therapy of prostatic adenoma stage I. However, its intake must be long and regular, otherwise recurrent clinical symptoms and further growth of prostatic adenoma are possible. 2 AUTHOR Lopatkin NA AUTHOR Roilans PJ AUTHOR Stoner E TITLE [The long-term treatment of patients with benign prostatic hyperplasia using Proscar] SOURCE Urol Nefrol (Mosk), ISS 1, 1996, P2-4 ABSTRACT The drug proskar (finasterid) has been developed and synthetized in "Merck Sharp & Dohme" research laboratories and tried initially in healthy male volunteers. Proskar is highly active as a blocker of 5-alpha-reductase blocking conversion of testosteron in dehydrotestosteron (DHT). The assessment of proskar effect on the prostate has been performed in 2000 patients throughout the world, including Russia. Follow-up studies (up to 5 years) demonstrate that proskar in the dose 5 mg/day produces a reduction in the levels of specific prostatic antigen, serum DHT and prostatic size, an increase in urination rate, life quality. In benign prostatic hyperplasia proskar realizes its effect in hormonal nature of the disease. The advantages are also safety and rare occurrence of side effects. The response became noticeable on the treatment month 6. 3 AUTHOR Geller J TITLE Five-year follow-up of patients with benign prostatic hyperplasia treated with finasteride. SOURCE Eur Urol; VOL 27, ISS 4, 1995, P267-73 ABSTRACT In 18 of 55 original patients who completed 5 years of treatment with finasteride, significant reductions in prostate size were noted at 1 year and sustained thereafter. Symptom scores in these same patients were significantly improved or stable over the 5 years while maximal urinary flow rates were unchanged. Data from 15 of 18 other patients who dropped out of the study before 5 years showed changes in prostate size, symptom score and flow rates that were similar to those noted in patients treated for 5 years. No side effects were noted in this study except for sexual dysfunction, which occurred in less than 5% of the patients. With few exceptions, finasteride appears to arrest the process of BPH over a 5 year period as indicated by sustained reductions in prostate size accompanied by either symptomatic improvement or stability in all other patients. 7 AUTHOR Kirby RS AUTHOR Bryan J AUTHOR Eardley I AUTHOR Christmas TJ AUTHOR Liu S AUTHOR Holmes SA AUTHOR Vale JA AUTHOR Shanmuganathan K AUTHOR Webb JA TITLE Finasteride in the treatment of benign prostatic hyperplasia. A urodynamic evaluation. SOURCE Br J Urol; VOL 70, ISS 1, 1992, P65-72 ABSTRACT A group of 69 men with bladder outflow obstruction due to benign prostatic hyperplasia (BPH) were treated in a double-blind, placebo-controlled study with finasteride (Proscar, MK-906), a 5-alpha reductase inhibitor, 5 mg or 10 mg/day or placebo for 3 months; subsequently, 20 patients received finasteride 5 mg/day for a further 9 months in an open extension study. In treated patients dihydrotestosterone declined by over 60%, remaining unchanged with placebo. Symptom scores fell significantly in all 3 groups. Mean maximum flow rates fell slightly in placebo-treated patients but improved by 1.5 ml/s in the 10 mg group and by 3.3 ml/s in the 5 mg group. After 1 year's treatment, the reduction in symptom score and increase in flow rate were well maintained; the mean prostate volume was reduced by 14% and prostatic specific antigen declined by 28%. It was concluded that finasteride shows some efficacy in the treatment of BPH, with minimal toxicity, but 12 months of therapy or longer may be necessary to achieve maximal effect. 1 AUTHOR Nickel JC AUTHOR Fradet Y AUTHOR Boake RC AUTHOR Pommerville PJ AUTHOR Perreault JP AUTHOR Afridi SK AUTHOR Elhilali MM TITLE Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study. SOURCE Can Med Assoc J 1996 Nov 1;155(9):1251-9 ABSTRACT OBJECTIVE: To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride. DESIGN: Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study. SETTING: Outpatient care in 28 centres across Canada. PARTICIPANTS: Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment. INTERVENTION: After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years. OUTCOME MEASURES: Efficacy: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. Safety: onset, course and resolution of all adverse events during the treatment period. RESULTS: In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters). CONCLUSION: Finasteride is a well-tolerated and effective alternative to watchful waiting in the treatment of moderate BPH. 4 AUTHOR Moore E AUTHOR Bracken B AUTHOR Bremner W AUTHOR Geller J AUTHOR Imperato-McGinley J AUTHOR McConnell J AUTHOR Roy J AUTHOR Tenover L AUTHOR Vaughan D AUTHOR Pappas F AUTHOR et al TITLE Proscar: five-year experience. SOURCE Eur Urol 1995;28(4):304-9 ABSTRACT We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH. 5 AUTHOR Stepanov VN AUTHOR Teodorovich OV AUTHOR Seregin AV AUTHOR Kadyrov ZA TITLE [The treatment of patients with benign prostatic hyperplasia with Proscar MSD (finasteride)] SOURCE Urol Nefrol (Mosk) 1995 Sep-Oct;(5):28-30 ABSTRACT 53 patients have undergone 1-year conservative treatment of benign prostatic hyperplasia with the drug proskar MSD. All the patients had the disease stage I-II, maximal urination rate at least 5 ml/s, residual urine to a maximum 150 ml. Benign nature of the disease was confirmed by the test with prostate-specific antigen. Selection of patients, follow-up and assessment of treatment results were conducted according to the scale of the International System of Overall Assessment of Prostatic Lesions. Proskar MSD was found active in benign prostatic hyperplasia basing on the shifts in the main three indices (symptom status, maximal urination rate, prostate size).