Impact of dutasteride on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH): a pooled analysis of three phase III studies

Purpose

To assess the impact of dutasteride compared with placebo on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, using pooled data from dutasteride phase III studies.

Methods

Nocturia was assessed using Question 7 of the International Prostate Symptom Score questionnaire. Efficacy measures included: mean change in nocturia at 24 months; proportion of patients with improvement/worsening in nocturia; nocturnal voiding frequency at baseline and study end, overall and by baseline subgroups; and nocturnal voiding frequency <2 at study end in patients with baseline score ≥2.

Results

In total, 4,321 patients with a mean age of 66 years were evaluated. From month 12 onwards, mean nocturia improvements were significantly superior with dutasteride than with placebo (p ≤ 0.05). Reduction in nocturia was significantly better with dutasteride than with placebo across all baseline subgroups tested (p ≤ 0.05). Also at month 24, dutasteride therapy resulted in a greater proportion of subjects with nocturia improvement compared with placebo (p ≤ 0.05), with the largest treatment group differences in subjects with a baseline nocturia score of 2 or 3. Among patients with significant nocturia at baseline (score ≥2), significantly more subjects with dutasteride versus placebo had a score <2 at month 24 (26 vs. 19 %, p < 0.001).

Conclusions

After 24 months of treatment, dutasteride treatment provided significantly greater improvements in nocturia, and less worsening, compared with placebo, primarily in subjects with two or three nocturia episodes per night. Studies specifically designed to assess nocturia are required to prospectively confirm these findings.     

Effects of Tadalafil on Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia and on Erectile Dysfunction in Sexually Active Men with Both Conditions: Analyses of Pooled Data from Four Randomized,Placebo‐Controlled Tadalafil Clinical Studies

IntroductionErectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging males and frequently occur together. Tadalafil has demonstrated efficacy in treating both conditions.AimThe study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men. We also assessed relationships of baseline disease severity and prostate specific antigen (PSA) to outcomes.MethodsData were pooled from four multinational, randomized studies of men ≥45 years with LUTS/BPH, with analyses restricted to sexually active men with ED. Randomization (baseline) followed a 4‐week placebo run‐in; changes from baseline were assessed vs. placebo using analysis of covariance.Main Outcome MeasuresInternational Prostate Symptom Score (IPSS), IPSS subscores, Quality‐of‐Life Index (IPSS‐QoL), BPH Impact Index (BII), and International Index of Erectile Function‐Erectile Function (IIEF‐EF) Domain score were used in this study.ResultsTadalafil (N = 505) significantly improved total IPSS vs. placebo (N = 521); mean changes from baseline were ?6.0 and ?3.6, respectively (P < 0.001). Improvements in IIEF‐EF Domain score (tadalafil, 6.4; placebo, 1.4) were also significant vs. placebo, as were the IPSS storage and voiding subscores, IPSS‐QoL, and BII (all P < 0.001).No significant impact of baseline ED severity or PSA category on IPSS response was observed (interaction P values, 0.463 and 0.149, respectively). Similarly, improvement in IIEF‐EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category (interaction P values, 0.926 and 0.230, respectively). Improvements in IPSS and IIEF‐EF Domain score during treatment were weakly correlated (r = ?0.229). Treatment‐emergent adverse events were consistent with previous reports.ConclusionsTadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions. Improvements in both conditions were significant regardless of baseline severity. Improvements in the total IPSS and the IIEF‐EF Domain score were weakly correlated. Porst H, Roehrborn CG, Secrest RJ, Esler A, and Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: Analyses of pooled data from four randomized, placebo‐controlled tadalafil clinical studies. J Sex Med 2013;10:2044–2052.     

The economic burden of prostate cancer

What's known on the subject? and What does the study add? Prostate cancer is the most common malignancy in men. Treatment is costly; the majority of men are treated with radiation or surgery, but even watchful waiting strategies are expensive. With increasing life expectancy more men are being diagnosed with prostate cancer, effectively increasing the economic burden of this disease. This study provides estimates of the cost of prostate cancer for different countries. These estimates could be used to populate models that explore economic costs of treating and preventing prostate cancer. Our review found considerable variation in costs across different countries, which may be due to differences in detection and management practices. In the present review we discuss expenditure on prostate cancer diagnosis, treatment and follow‐up and evaluate the cost of prostate cancer and its management in different countries. Prostate cancer costs were identified from published data and internet sources. To provide up‐to‐date comparisons, costs were inflated to 2010 levels and the most recent exchange rates were applied. A high proportion of the costs are incurred in the first year after diagnosis; in 2006, this amounted to 106.7–179.0 million euros (€) in the European countries where these data were available (UK, Germany, France, Italy, Spain and the Netherlands). In the USA, the total estimated expenditure on prostate cancer was 9.862 billion US dollars ($) in 2006. The mean annual costs per patient in the USA were $10 612 in the initial phase after diagnosis, $2134 for continuing care and $33 691 in the last year of life. In Canada, hospital and drug expenditure on prostate cancer totalled C$103.1 million in 1998. In Australia, annual costs for prostate cancer care in 1993–1994 were 101.1 million Australian dollars. Variations in costs between countries were attributed to differences in incidence and management practices. Per patient costs depend on cancer stage at diagnosis, survival and choice of treatment. Despite declining mortality rates, costs are expected to rise owing to increased diagnosis, diagnosis at an earlier stage and increased survival. Unless new strategies are devised to increase the efficiency of healthcare provision, the economic burden of prostate cancer will continue to rise.     

Nocturia improvement in the combination of Avodart® and tamsulosin (CombAT) study

Purpose

The purpose of the study was to assess the impact of dutasteride plus tamsulosin combination therapy, compared with dutasteride or tamsulosin monotherapy, on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) using data from the 4-year CombAT study.

Methods

Nocturia was assessed using Question 7 of the International Prostate Symptom Score questionnaire. Efficacy measures included as follows: mean change in nocturia at 3-month intervals up to 48 months; proportion of patients with improvement/worsening in nocturia; nocturnal voiding frequency at baseline and study end, overall and by baseline subgroups; and nocturnal voiding frequency <2 at study end in patients with a baseline score ≥2.

Results

In total, 4,722 patients with a mean age of 66 years were included. Mean nocturia improvements were significantly superior (p ≤ 0.01) with combination therapy than with either monotherapy (adjusted mean change from baseline in IPSS Question 7 score at month 48: combination therapy ?0.5, dutasteride ?0.4, tamsulosin ?0.3). Reduction in nocturia score with combination therapy was significantly (p ≤ 0.01) better than tamsulosin monotherapy across all baseline subgroups tested, except for men with previous 5ARI use. Among those with a baseline IPSS Q7 score ≥2, more patients with combination therapy had a score <2 at month 48 (34 %) compared with dutasteride (30 %, p = 0.018) or tamsulosin (26 %, p < 0.0001).

Conclusions

Combination therapy provided greater improvements and less worsening of nocturia compared with both dutasteride and tamsulosin monotherapies. These analyses are the first to show greater improvement with a 5ARI/α-blocker combination versus either agent alone for the management of nocturia in patients with LUTS/BPH.