Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder.

OBJECTIVE: To assess in a phase 3a trial the efficacy of solifenacin succinate, a once-daily oral antimuscarinic agent in development at 5-mg and 10-mg dosage strengths, for the treatment of overactive bladder (OAB) (Yamanouchi Pharmaceutical Co. Ltd, Tokyo, Japan) compared with placebo in patients with symptoms of OAB, i.e. urgency, incontinence, and frequency, with additional objectives being to assess the safety and tolerability of solifenacin and to compare the efficacy and safety of solifenacin with tolterodine 2 mg twice daily. PATIENTS AND METHODS: The study was an international, multicentre, randomized, double-blind, tolterodine- and placebo-controlled trial conducted at 98 centres. Adult patients with symptomatic OAB for > or = 3 months were eligible; after a single-blind 2-week placebo run-in period patients were randomized equally to a 12-week double-blind treatment with either tolterodine 2 mg twice daily, placebo, solifenacin 5 mg or 10 mg once daily. Efficacy variables included change from baseline in the mean number of urgency, incontinence and urge incontinence episodes, and change from baseline in voids/24 h and mean volume voided/void. RESULTS: In all, 1281 patients were enrolled, 1081 randomized and 1077 treated; 1033 were evaluated for efficacy. Compared with placebo, the change from baseline (-1.41, -32.7%) in the mean number of urgency episodes per 24 h was statistically significantly lower with solifenacin 5 mg (-2.85, -51.9%) and 10 mg (-3.07, -54.7%; both P < 0.001), but not with tolterodine (-2.05, -37.9%; P = 0.0511). There was a statistically insignificant decrease in episodes of incontinence with tolterodine (-1.14; P = 0.1122) but a significant decrease in patients treated with solifenacin 5 (-1.42; P = 0.008) and 10 mg (-1.45; P = 0.0038). Compared with placebo (-1.20, -8.1%) the mean number of voids/24 h was significantly lower in patients receiving tolterodine (-1.88, -15%; P = 0.0145), solifenacin 5 (-2.19, -17%) and 10 mg (-2.61, -20%; both P < 0.001). The mean volume voided/void was also significantly higher with all three active treatments (P < 0.001). Solifenacin was well tolerated; compared with placebo (4.9%), dry mouth (the most common side-effect), mostly mild, was reported in 18.6% of patients receiving tolterodine, 14.0% receiving 5 mg and 21.3% receiving 10 mg solifenacin. CONCLUSION: Solifenacin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and was associated with an acceptable level of anticholinergic side-effects. Solifenacin demonstrated significantly favourable efficacy to side-effect ratio in treating symptomatic OAB.

Orchidectomy prior to definitive radiotherapy for localized prostatic cancer.

PURPOSE: To identify potential survival benefits of cytoreductive orchidectomy performed prior to definitive radiation for localized prostate cancer. METHODS AND MATERIALS: Between 1977-1988, all patients with localized prostatic cancer from the Wellington Region received definitive radiotherapy (n = 200). One referring urologist Peter M. Meffen (P.M.M.) had commenced a program of prior orchidectomy followed by definitive radiation treatment (median time to radiation therapy was 5 months, n = 30). RESULTS: Five-year overall survival (OS) and relapse-free survival (RFS) for each stage were Stage A 82%, and 82%; Stage B 75%, and 61%; Stage C 57%, and 38%, respectively. Ten-year OS and RFS for each stage were Stage A 78%, and 72%; Stage B 51%, and 18%; Stage C 32% and 0%, respectively. Multivariate analysis identified prior orchidectomy treatment and histological grade as independently significant prognostic factors for OS and RFS. Factors influencing RFS were clinical stage, prior orchidectomy, and histological grade. Prior orchidectomy was associated with an increase in OS at 5 years when compared to those patients receiving radiotherapy alone, 86% vs. 69%, and maintained at 10 years, 82% vs. 46% (p < 0.05). The two groups were comparable by stage, histological grade, and age. There were no changes in the referral pattern during the study period. CONCLUSIONS: Our results suggest that prior cytoreduction by orchidectomy has a beneficial effect on OS and RFS for patients with localized prostate cancer. It is unclear whether survival benefits are due to the cytoreductive therapy, the adjuvant therapy, or a combination of both. Further study in this area is warranted, ideally in the form of randomized prospective clinical trials.

The effect of finasteride on prostate volume, urinary flow rate and symptom score in men with benign prostatic hyperplasia.

This study was designed to determine the efficacy of the 5 alpha-reductase inhibitor finasteride (Proscar, MK-906) in men with reduced urinary flow rates and symptoms of urinary outflow obstruction secondary to benign prostatic hyperplasia. Forty-five men were randomized to one of three groups receiving either placebo, 1 mg/day or 5 mg/day finasteride for the first 12 months of the study period. At the end of this period all men received 5 mg/day finasteride for a further 2 years. Efficacy was determined by measurement of prostate volume, maximum urinary flow rate, and symptom score using a modified Boyarsky assessment. Prostate volume reduced by 20 and 27%, respectively, for those on 1 and 5 mg after the first year. At 3 years the volume had reduced by 43%. This reduction in prostate volume was associated with an improvement in maximum urinary flow rate by 50% (1 mg), and 35% (5 mg) at 1 year, and 36% at 3 years. The total, obstructive and non-obstructive symptom scores decreased (improved) for patients on 1 and 5 mg finasteride, with the total score reducing by 33% from baseline at year 3. The results demonstrate that finasteride causes a modest but significant clinical improvement in men with urinary outflow obstruction secondary to benign prostatic hyperplasia.

Familial cystic nephroma and pleuropulmonary blastoma.

BACKGROUND: Cystic nephroma (CN) and pleuropulmonary blastoma (PPB) are rare tumors without any previously recognized familial association. METHODS: Two cases of CN and one case of PPB in three siblings are reported. RESULTS: A 27-month-old girl and a 31-month-old boy underwent nephrectomy for CN and are free of disease in the contralateral kidney 16 and 14 years later, respectively. Their 28-month-old sister underwent pleuropneumonectomy with postoperative chemotherapy for PPB and died of recurrent disease 9 months later. CONCLUSION: To the knowledge of the authors, these cases represent the first reported familial occurrence of CN and the second of CN and PPB among siblings. The inheritance of a germline mutation predisposing to the development of these tumors is postulated.

The value of early diagnosis in the treatment of patients with testicular cancer.

A study of 79 patients treated at Wellington Hospital for testicular cancer showed that those presenting with a short history (time from tumour recognition to surgery) had no better prognosis than those with a longer history (chi 2 = 1.857, p = 0.173). Tumour size was significantly related to this time interval such that those patients with a short history were more likely to have smaller tumours (rp = 0.651, p = 0.001). The data suggests that testicular tumours are currently being recognised too late in their development to allow any improvement in survival to be gained from reducing the interval from recognition to treatment. However, earlier recognition of the tumour by the patient may allow diagnosis and treatment in an earlier stage. The advantages of diagnosis in early stage disease are substantial and the need for a public education programme involving testicular self examination to allow early diagnosis is discussed.

Effect of abdominal straining on urinary flow rate in normal males.

The measurement of urinary flow rate by uroflowmetry and its relationship to voided volume and age have been extensively studied. It is well recognised that some men void with abdominal straining, but any effect of this on the urinary flow rate is usually not taken into account in urological practice. The aim of this study was to determine whether abdominal straining had any significant influence on the urinary flow rate. Three male volunteers performed multiple voidings either with or without abdominal straining. Statistical transformation of the data and the use of co-variant analysis allowed a comparison between "normal" or passive voiding and voiding with abdominal straining. The results showed that abdominal straining caused a significant improvement in both the average and maximum urinary flow rate. If the effect of abdominal straining is not taken into account during the interpretation of uroflowmetry results, incorrect conclusions may be made which could influence subsequent management. It is suggested that the method of voiding should be standardised by instructing patients, if possible, to avoid abdominal straining during uroflowmetry assessment.

Orchiectomy and delayed radiotherapy as treatment for prostatic carcinoma. A 10-year survey.

One hundred and fifty patients with carcinoma of the prostate treated between 1967 and 1982 have been reviewed. Thirty-three patients were treated with stilboestrol alone, 36 by orchiectomy alone and in 81 cases radical radiotherapy was given to the prostate (and in 10 of the 81 cases to the regional and para-aortic lymph nodes) 5 or 6 months after orchiectomy. Although there was no significant difference between the results of those treated by stilboestrol alone and those treated by orchiectomy alone, in those patients receiving orchiectomy and delayed radiotherapy there was a significant improvement in survival. If patients with Stage D disease are excluded, this is a highly significant difference and indeed the survival in these patients does not differ significantly from the expected survival at this age. The 5-year survival rate of Stage D patients treated by this method was 35%.