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The Medical Therapy Of Prostatic Symptoms (MTOPS) Trial: Results

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Medical Treatment of BPH: The Challenge
BPH is the most common benign neoplasm in older men Clinical BPH involves benign prostatic enlargement, lower urinary tract symptoms (LUTS), and bladder outlet obstruction BPH can interfere with daily activities and can diminish health-related quality of life specific to urinary symptoms

BPH=benign prostatic hyperplasia Adapted from Bautista OM et al Control Clin Trials 2003;24:224-243; Emberton M et al Urology 2003;61(2):267-273; Girman CJ et al Eur Urol 1999;35:277-284. Slide 2

Downlaoded from www.com. Slide 3 .proscar.pk Recommendations of the 5th International Consultation on BPH in 2001 Medical Treatment of Clinical BPH Short-term Long-term Improve symptoms Prevent complications Minimize adverse effects of treatment Preserve quality of life Overall Adapted from Chatelain C et al 5th International Consultation on BPH 2001:519-535.

Slide 4 .Downlaoded from www.proscar.pk Recommendations of the 5th International Consultation on BPH in 2001 Medical Treatment of Clinical BPH 5-alpha reductase inhibitors and alpha blockers are the only recommended medical treatments of BPH Recommendations for phytotherapy or polyene derivatives require additional long-term data Adapted from Chatelain C et al 5th International Consultation on BPH 2001:519-535.com.

com. NIH Publication No. 99-4303.proscar. Slide 5 .Downlaoded from www. increase urinary flow rate. National Cancer Institute. 1999.11:17-25. and prevent BPH outcomes by reducing prostate enlargement through hormonal mechanisms Adapted from Roehrborn CG Curr Opin Urol 2001.pk Could Combination Therapy Be a Better Approach? Two-Drug Therapy Activates Two Distinct and Complementary Mechanisms of Action Alpha blockers Improve symptoms and increase urinary flow rate by relaxing prostatic and bladder-neck smooth muscle through sympathetic activity blockade 5-Alpha reductase inhibitors Improve symptoms.

34:169-175. Debruyne FMJ et al Eur Urol 1998. Slide 6 . Inc. PROSCAR vs. Lepor H et al N Engl J Med 1996.335(8):533-539. placebo-controlled. PREDICT=Prospective European Doxazosin and Combination Therapy Adapted from Roehrborn CG Curr Opin Urol 2001.11:17-25..proscar.61(1):119-126. PROSCAR® vs. Savage SJ et al Can J Urol 1998..5(3):578-584. multicenter. doxazosin vs.com. combination in 1095 men with BPH in Europe PROSCAR (finasteride) is a registered trademark of Merck & Co.Downlaoded from www. USA. Whitehouse Station.pk Evidence on Combination Therapy Most trials of 5-alpha reductase inhibitor + alpha-blocker therapy were of short duration or lacked placebo controls Two randomized. terazosin vs. 12-month studies showed that combination therapy did not enhance the efficacy of alpha-blocker monotherapy in terms of improving symptoms or urinary flow rate – VA COOP: Placebo vs. Kirby RS et al Urology 2003. NJ. VA COOP=Veterans Affairs Cooperative. combination in 1229 men with BPH in US VA system – PREDICT: Placebo vs.

proscar. the alpha blocker doxazosin. Slide 7 . or their combination would prevent or delay the clinical progression of BPH Independently Conducted by the US National Institutes of Health (NIH) Adapted from Bautista OM et al Control Clin Trials 2003.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Objective of MTOPS To determine whether long-term medical therapy with PROSCAR®.24:224-243.com.Downlaoded from www.

placebo-controlled. Qmx =maximum urinary flow a Adapted from Bautista OM et al Control Clin Trials 2003. randomized Average follow-up: 4.com.24:224-243.proscar. Slide 8 .Downlaoded from www.5 years Randomized N=3047 • • • • Men ≥ 50 years of age AUA symptom score 8–30 Qmx 4–15 ml/sec a Voided volume ≥ 125 ml Entry Criteria Doxazosin (n=756) PROSCAR® (n=768) PROSCAR + doxazosin (n=786) Placebo (n=737) AUA=American Urological Association.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Study Design: Overview Double-blind. multicenter.

Downlaoded from www. AUR=acute urinary retention Adapted from Bautista OM et al Control Clin Trials 2003.proscar. Slide 9 .24:224-243.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Study Design: Outcomes Primary outcome Clinical progression of BPH – Confirmed ≥ 4-point increase in AUA-SI – AUR – Recurrent urinary tract infections/ urosepsis – Urinary incontinence – Renal insufficiency – – – – – BPH symptoms Qmx a Prostate volume Sexual function Quality of life Natural history of BPH with respect to Secondary outcome AUA-SI=American Urological Association Symptom Index.com.

proscar.0 31.6 No significant differences between groups AUA=American Urological Association.349(25):2385-2396.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Baseline Characteristics of Patients Characteristic Age (years) AUA-SI score TRUS Prostate volume (cc) Postvoid residual urine volume (ml) Qmax (ml/second) Value* 62.0 39.com.0 17.Downlaoded from www. Slide 10 . TRUS=transrectal ultrasound *Values are medians Adapted from McConnell JD et al N Engl J Med 2003.0 10.

001) p<0.0 2.com. Slide 11 .Downlaoded from www.5 Years from randomization P values are for the comparison with placebo.5 1.001 0 0.5 3.001 p<0.0 4.0 3.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Impact of Medical Therapy on Clinical Progression of BPH Cumulative incidence of BPH progression 25 Placebo (n=737) PROSCAR® (n=768) Doxazosin (n=756) Combination (PROSCAR + doxazosin) (n=786) Percentage with event 20 15 p=0. Adapted from McConnell JD et al N Engl J Med 2003.0 5. Bautista OM et al Control Clin Trials 2003.002 10 5 0 66% risk reduction (p<0.24:224-243.5 5.5 4.proscar.5 2.0 1.349(25):2385-2396.

Slide 12 .pk MTOPS (Medical Therapy Of Prostatic Symptoms) Most BPH Progression Events Were Due to Symptom Progression Distribution of BPH progression events Incontinence 7% AUR 12% >4-point AUA-SI increase 80% UTI/urosepsis 1% Renal insufficiency 0% UTI=urinary tract infection Adapted from McConnell JD et al N Engl J Med 2003.com.Downlaoded from www.349(25):2385-2396.proscar.

0 2. May 2002. Florida.Downlaoded from www.0 5.5 3.5 4.proscar.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Impact of Medical Therapy on Symptom Control Cumulative incidence of ≥ 4-point increase in symptom score* 25 Percentage with event 20 15 10 5 0 Placebo (n=737) PROSCAR® (n=768) Doxazosin (n=756) Combination (PROSCAR + doxazosin) (n=786) 64% risk reduction (p<0.com.5 5. USA.5 1. Slide 13 .5 2.0 1.24:224-243.5 Years from randomization *AUA-SI score Adapted from McConnell JD. Bautista OM et al Control Clin Trials 2003.0 4. Presentation at AUA Annual Meeting. Orlando.0001) 0 0.0 3.

Orlando. May 2002.com.001 vs.24:224-243.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Effect of Medical Therapy on Prostate Volume Change from baseline in prostate volume –13%* –16%* Doxazosin (n=756) Combination (PROSCAR® + doxazosin) (n=786) PROSCAR (n=768) +18% +18% 0 10 20 Placebo (n=737) –20 –10 Median % change from baseline *p<0. Bautista OM et al Control Clin Trials 2003. Florida. Slide 14 .proscar.Downlaoded from www. Presentation at AUA Annual Meeting. USA. baseline Adapted from McConnell JD.

proscar.009 risk reduction (p<0.5 2. Bautista OM et al Control Clin Trials 2003.5 Placebo (n=737) PROSCAR® (n=768) Doxazosin (n=756) Combination (PROSCAR + doxazosin) (n=786) Percentage with event 3.5 4.com.5 2.0 1.0 1.0 0.5 3.349(25):2385-2396.0 2. Slide 15 .24:224-243.5 Years from randomization Adapted from McConnell JD et al N Engl J Med 2003.001) p<0.0 2.5 0 0 0.5 1.0 3.5 81% p=0.Downlaoded from www.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Impact of Medical Therapy on the Risk of AUR Cumulative incidence of AUR 3.0 5.001 1.5 5.0 4.

transurethral prostatectomy) or open surgeries primarily.001 p<0.0 1. other therapies were minimally invasive (e.24:224-243.g.349(25):2385-2396.5 Years from randomization *Endoscopic (e.5 2. Bautista OM et al Control Clin Trials 2003.5 5.com.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Impact of Medical Therapy on the Need for Invasive BPH Therapy* Cumulative incidence of BPH-related surgery 10 Placebo (n=737) PROSCAR® (n=768) Doxazosin (n=756) Combination (PROSCAR + doxazosin) (n=786) Percentage with event 8 6 4 2 0 67% p<0..001 risk reduction (p<0.5 3.5 1. transurethral microwave therapy) Adapted from McConnell JD et al N Engl J Med 2003.proscar. Slide 16 .0 5.001) 0 0.0 4.g.Downlaoded from www..0 3.5 4.0 2.

proscar.6 2.1** 5.7 0.1 0.8** 3600 4.9** 0. 2002.2** 2.3 2.6 0.5 0.7 0.2** 0.0** 4.8** *The numbers shown are the rates per 100 person-years of follow-up (incidence density) as of September 30.3 2.4** 4.6 1.9 0.6 0. Bautista OM et al Control Clin Trials 2003.3** 4. placebo Adapted from McConnell JD et al N Engl J Med 2003.com.3** 1.5** 2.4 3832 5.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Medical Monotherapy and Combination Therapy Demonstrated Long-Term Tolerability Ten most frequent adverse events among groups* Placebo (n=737) PROSCAR Doxazosin PROSCAR™ (n=756) (n=768) and doxazosin (n=786) Variable Total no.6 4.4 3652 3.05 vs. **p<0.4 0.3 2.9 0.Downlaoded from www.24:224-243.1** 1.8 0.3 2.6 1.6 0.8** 0.5** 3. of person-years Adverse Event Erectile dysfunction Dizziness Postural hypotension Asthenia Decreased libido Abnormal ejaculation Peripheral edema Dyspnea Allergic reaction Somnolence 3489 3.1 1.349(25):2385-2396.4** 4.1** 1.4** 1. Slide 17 .7 0.

001*) – 64% reduction in worsening symptoms (p<0.349(25):2385-2396.001*) – 67% reduction in need for invasive BPH therapy (p<0.001*) – 81% reduction in risk of AUR (p<0.pk MTOPS (Medical Therapy Of Prostatic Symptoms) Conclusions Combination therapy is the most effective form of medical therapy for BPH – 66% reduction in risk of BPH progression (p<0. placebo at 4 years Adapted from McConnell JD et al N Engl J Med 2003. Slide 18 .proscar.001*) Long-term monotherapy and combination therapy were well tolerated and effective *vs.com.Downlaoded from www.

Nyberg Jr. Slide 19 . PhD.com.pk The Future of Combination Therapy for BPH “The evidence supporting combination therapy [for BPH] in selected patients is so strong that I expect to see major changes in medical practice in the near future.” Leroy M.htm. Available at: http://www.gov/news/pr/may2002/niddk-28. MD Director.nih.proscar.Downlaoded from www. Urology Program National Institute of Diabetes and Digestive and Kidney Diseases Adapted from NIH news release.

proscar.com.Downlaoded from www. Slide 20 .pk References Please refer to notes page.

All rights reserved. Whitehouse Station.proscar. NJ. 3-05 PSC 2004-W-14295-SS Printed in USA VISIT US ON THE WORLD WIDE WEB AT http://www.com. Copyright © 2004 Merck & Co. USA.pk MTOPS: Medical Therapy Of Prostatic Symptoms Before prescribing any of the products mentioned in this slide presentation.. please consult the manufacturers’ prescribing information.. Inc.merck.com Slide 21 .Downlaoded from www.

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