Medical Treatment

Long-term Sustained Improvement in Symptoms of Benign Prostatic Hy-

perplasia With the Dual 5�-Reductase Inhibitor Dutasteride: Results of

4-Year Studies

Roehrborn CG, Lukkarinen O, Mark S, et al (UT Southwestern Med Ctr, Dallas;Univ of Oulu, Finland; St George’s Hosp, Christchurch, New Zealand; et al)BJU Int 96:572-577, 2005 12–12

Objective.—To report additional analyses of efficacy over the initial 2years and during a 2-year open-label extension of the three pivotal phase 3studies in which dutasteride, a dual inhibitor of type 1 and 2 5�-reductase,was shown to be effective and well tolerated.

Patients and Methods.—All patients in the placebo and active groupswere eligible for entry into the 2-year open-label extension, with all receivingdutasteride 0.5 mg daily. Mean changes from baseline were calculated forthe American Urologic Association Symptom Index (AUA-SI) score at eachscheduled time in the double-blind and open-label phase. The additionalanalyses included a breakdown of the AUA-SI score, including stratifyingpatients by symptom severity, assessment by baseline age and prostate vol-ume, and the evaluation of symptoms responders.

Results.—There was a clinically meaningful improvement in AUA-SI inpatients on dutasteride in the double-blind phase, but not in those on pla-cebo. At 48 months, patients on dutasteride in both study phases had greaterimprovements in AUA-SI score and individual question scores than those ondutasteride in the open-label phase only. The proportion of patients with se-vere symptoms declined in both study groups, although these changes weremore profound in those receiving dutasteride for the 4-year duration of thestudy.

Conclusion.—In men with symptomatic benign prostatic hyperplasia,long-term (4-year) treatment with the dual isozyme 5�-reductase inhibitordutasteride resulted in sustained and continued improvements in symptomsand flow rate. For 4 vs 2 years, longer dutasteride therapy resulted in greatersymptom improvement.

� The second 5�-reductase inhibitor on the market, dutasteride, differs fromfinasteride in that it inhibits both the 5�-reductase type II and type I. It has longbeen known that 5�-reductase type I is less prevalent in benign prostatic hy-perplasia tissue, but it has been suggested that it is found with increasing fre-quency in prostate cancer tissue.

In the pivotal phase III, placebo-controlled trials with dutasteride suggestedthat dutasteride exerts a superior efficacy compared with placebo that ap-pears to be at least comparable to finasteride in terms of symptom and flowrate improvement, volume reduction, and other outcome parameters.

This particular trial reports on the open-label extension studies in which pa-tients who finished the 2-year placebo-controlled trial were allowed to con-tinue on open-label dutasteride 0.5 mg daily. An intriguing finding shown in Fig-

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102 � Urology

ure 2 on page 574 in the article suggests that, in fact. from year 2 to year 4, thepatients originally treated with dutasteride had continuing improvement in theIPSS and at all time points outperformed the originally placebo-treated pa-tients even after they were switched to dutasteride. Similar observations havebeen made regarding the improvements in maximum urinary flow rate. It isintriguing to speculate why in the open-label dutasteride studies a continuingimprovement in symptoms is observed from year 2 to year 4, which had notbeen observed in any of the other open-label trials conducted with finasterideor other medical therapy for BPH.

I believe that one possible explanation is the patient population enrolled inthe dutasteride phase III trials. Remember that the patients enrolled in thephase III trials program were those with larger prostates, namely, more than30 g, and higher serum PSA levels, namely, more than 1.5 ng/mL. Therefore, itseems possible that these patients have a greater potential for long-term im-provement on the basis of a larger gland and a greater amount of glandular epi-thelial tissue that could be affected by dihydrotestosterone and in turn by itsdecrease as a result of 5 AR inhibition. Although this is an unproved hypothe-sis, it is difficult to otherwise explain the continuing effect of dutasteride in thisopen-label extension study.

C. G. Roehrborn, MD

Combination Therapy With Doxazosin and Finasteride for Benign Pros-

tatic Hyperplasia in Patients With Lower Urinary Tract Symptoms and a

Baseline Total Prostate Volume of 25 ml or Greater

Kaplan SA, for the Medical Therapy of Prostatic Symptoms (MTOPS) ResearchGroup (Columbia Univ, New York; et al)J Urol 175:217-221, 2006 12–13

Purpose.—We examined data from the Medical Therapy of ProstaticSymptoms trial to determine the relationship between baseline TPV and theeffect of medical therapy in men with LUTS secondary to BPH.

Materials and Methods.—A total of 3,047 patients with LUTS were ran-domized to placebo, 4 to 8 mg doxazosin, 5 mg finasteride or the combina-tion of doxazosin and finasteride. Average treatment duration was 4.5 yearsThe primary outcome was time to overall clinical progression of BPH, de-fined as a confirmed 4 point or greater increase in AUA SS, acute urinary re-tention, incontinence, renal insufficiency or recurrent urinary tract infec-tion. Secondary outcomes were the need for invasive therapy for BPH, andchanges in AUA SS and the maximum urinary flow rate with time. TPV wasmeasured by transrectal ultrasound at baseline and study end.

Results.—In patients with a small prostate (baseline TPV less than 25 ml)combination therapy was no better than doxazosin alone for decreasing therisk of clinical progression of BPH and need for invasive therapy as well asimproving AUA SS and the maximum urinary flow rate. However, in pa-tients with moderate size (25 to less than 40 ml) or enlarged (40 ml or

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Chapter 12–Benign Prostatic Hyperplasia � 103