An Evaluation of Sexual Function in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia in Men Treated with the Temporarily Implanted Nitinol Device.

Purpose: To document the effect of the temporarily implanted nitinol device (iTind; Medi-Tate Ltd, Israel) on sexual function from a multicenter, randomized, single-blinded, sham-controlled trial. Materials and Methods: Men were randomized 2:1 between iTind and sham procedure arms. The iTind was placed for 5-7 days and an 18F Foley catheter was inserted and removed for the iTind and sham group, respectively. Patients were assessed at baseline, 3, and 12 months postoperatively using the Sexual Health Inventory for Men (SHIM) and International Index of Erectile Function (IIEF). Unblinding occurred at 3 months. Results: We studied 185 men with a mean age of 61.1 ± 6.5 years. There was no difference in SHIM or total IIEF between iTind and sham at 3 months or in the iTind arm at 12 months compared with baseline. Men in the iTind arm without erectile dysfunction at baseline showed an improvement in total IIEF score of +6.07 ± 21.17 points (p = 0.034) at 12 months, in addition to an improvement in ejaculatory function. SHIM scores remained unchanged in all groups, regardless of age, prostate volume, or baseline erectile function. Conclusion: No changes were observed in sexual and ejaculatory function of patients with iTind regardless of a man's age, prostate volume, and baseline sexual function. Clinicaltrials.gov: NCT02506465.

The iTind Temporarily Implanted Nitinol Device for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Multicenter, Randomized, Controlled Trial.

OBJECTIVE: To report the results of a multicenter, randomized, controlled trial with a temporarily implanted nitinol device (iTind; Medi-Tate Ltd, Hadera, Israel) compared to sham for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: Men 50 years or older were randomized 2:1 between iTind and sham procedure arms. A self-expanding, temporary nitinol device was placed for 5-7 days and an 18F Foley catheter was inserted and removed for the iTind and sham group, respectively. Patients were assessed at baseline, 1.5, 3, and 12 months postoperatively using the IPSS, peak urinary flow rate, residual urine, quality of life, and the International Index of Erectile Function. Unblinding occurred at 3 months. RESULTS: A total of 175 men (mean age 61.1 ± 6.5) participated (118 iTind vs 57 sham). A total of 78.6% of patients in the iTind arm showed a reduction of ≥3 points in IPSS, vs 60% of patients in the control arm at 3 months. At 12 months, the iTind group reported a 9.25 decrease in IPSS (P< .0001), a 3.52ml/s increase in peak urinary flow rate (P < .0001) and a 1.9-point reduction in quality of life (P < .0001). Adverse events were typically mild and transient, most Clavien-Dindo grade I or II, in 38.1% of patients in the iTind arm and 17.5% in the control arm. No de novo ejaculatory or erectile dysfunction occurred. CONCLUSION: Treatment with the second-generation iTind provided rapid and sustained improvement in lower urinary tract symptoms for the study period while preserving sexual function.

Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer.

BACKGROUND: This open-label, multicenter, dose-escalation study evaluated multiple dose levels of immunotherapy in patients with metastatic hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, consisted of 2 allogeneic prostate-carcinoma cell lines modified to secrete granulocyte-macrophage-colony-stimulating factor (GM-CSF). METHODS: Dose levels ranged from 100 x 10(6) cells q28d x 6 to 500 x 10(6) cells prime/300 x 10(6) cells boost q14d x 11. Endpoints included safety, immunogenicity, overall survival, radiologic response, prostate-specific antigen (PSA) kinetics, and serum GM-CSF pharmacokinetics. RESULTS: Eighty men, median age 69 years (range, 49-90 years), were treated. The most common adverse effect was injection-site erythema. Overall, the immunotherapy was well tolerated. A maximal tolerated dose was not established. The median survival time was 35.0 months in the high-dose group, 20.0 months in the mid-dose, group, and 23.1 months in the low-dose group. PSA stabilization occurred in 15 (19%) patients, and a >50% decline in PSA was seen in 1 patient. The proportion of patients who generated an antibody response to 1 or both cell lines increased with dose and included 10 of 23 (43%) in the low-dose group, 13 of 18 (72%) in the mid-dose group, and 16 of 18 (89%) in the high-dose group (P = .002; Cochran-Armitage trend test). CONCLUSIONS: This immunotherapy was well tolerated. Immunogenicity and overall survival varied by dose. Two phase 3 trials in patients with metastatic HRPC are underway.

Vardenafil in patients with erectile dysfunction: achieving treatment optimization.

This post hoc analysis of data from a multicenter, randomized, double-blind study determined how many attempts were needed to record at least 1 successful penetration and maintenance of erection long enough for successful intercourse in a broad population of men with erectile dysfunction taking vardenafil at 5, 10, or 20 mg or placebo. The cumulative probability of achieving successful penetration and of maintaining an erection increased with the number of attempts for all 3 vardenafil groups. For the first attempt, the probability of achieving successful penetration was higher in all 3 vardenafil groups compared with placebo; 67% in the 5-mg vardenafil group, 77% in the 10-mg vardenafil group, and 74% in the 20-mg vardenafil group compared with 46% for placebo. By the third attempt, the probability of at least 1 success was 82% for 5, 88% for 10, and 85% for 20 mg vardenafil compared with 68% for placebo. The probability of maintaining an erection long enough to complete intercourse at the first attempt was 51% for 5, 69% for 10, and 61% for 20 mg vardenafil compared with 28% for the placebo group. By the third attempt, the probability of maintaining an erection was 66% for 5, 81% for 10, and 77% for 20 mg vardenafil in contrast to 53% for placebo. The results of this analysis indicate that patients without initial treatment success should continue treatment or increase the dose because the cumulative probability of success increases with additional attempts with vardenafil, with a plateau at about the fourth dose.

Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia.

OBJECTIVES: To assess the long-term safety and efficacy of dutasteride, a dual type 1 and type 2 5-alpha-reductase inhibitor, in the treatment of symptomatic benign prostatic hyperplasia and associated lower urinary tract symptoms. METHODS: Data from two Phase IIIa multicenter, randomized, placebo-controlled trials of 2-year duration plus a 2-year open-label extension were pooled and analyzed. The entry criteria included age 50 years old or older, clinical diagnosis of benign prostatic hyperplasia, prostate volume of 30 cm3 or greater, American Urological Association symptom score of 12 or greater, peak urinary flow rate of 15 mL/s or less, and prostate-specific antigen level of 1.5 ng/mL or greater but less than 10 ng/mL. RESULTS: A total of 2802 men were randomized into the double-blind phase of the two studies with 1908 patients (68%) completing the study. Of these, 1570 subjects were enrolled in the open-label phase, and 569 subjects received dutasteride for 48 months. Changes at the 48-month visit for dutasteride/dutasteride-treated subjects included improvement in prostate volume (-26.2%), American Urological Association Symptom Index (-6.1 points), and peak urinary flow rate (+2.8 mL/s). Changes for the placebo/dutasteride group included prostate volume (-20.7%), American Urological Association Symptom Index (-5.3 points), and peak urinary flow rate (+1.8 mL/s). Acute urinary retention and surgery occurred in a small percentage of subjects (less than 2% and less than 1%) in the open-label extension phase. Dutasteride was well tolerated with no statistically significant increase in drug-related adverse events during the open-label extension and no adverse laboratory trends. CONCLUSIONS: Dual inhibition of 5-alpha-reductase with dutasteride provided sustained efficacy in subjects with symptomatic benign prostatic hyperplasia treated for 48 months. Near-complete, long-term suppression of dihydrotestosterone (93% at 48 months) with dutasteride did not lead to an increase in adverse events compared with that reported in the 2-year period.

A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer.

PURPOSE: We compared the endocrinological and biochemical efficacy of abarelix depot, a gonadotropin-releasing hormone antagonist, with that of a widely used combination of luteinizing hormone releasing hormone agonist and a nonsteroidal antiandrogen. MATERIALS AND METHODS: A total of 255 patients were randomized to receive open label 100 mg. abarelix depot or 7.5 mg. leuprolide acetate intramuscularly injection on days 1, 29, 57, 85, 113 and 141 for 24 weeks. Patients in the abarelix group received an additional injection on day 15 and those in the leuprolide acetate group received 50 mg. bicalutamide daily. Patients could continue treatment with study drug for an additional 28 weeks. The efficacy end points were the comparative rates of avoidance of testosterone surge (greater than 10% increase) within 7 days of the first injection and the rapidity of achieving reduction of serum testosterone to castrate levels (50 ng./dl. or less) on day 8. Patients were monitored for adverse events and laboratory abnormalities. RESULTS: Abarelix was more effective in avoidance of testosterone surge (p <0.001) and the rapidity of reduction of testosterone to castrate levels on day 8 (p <0.001) than combination therapy. No significant difference was seen between the groups in the initial rate of decline of serum prostate specific antigen or the ability to achieve and maintain castrate levels of testosterone. No unusual or unexpected adverse events were reported. CONCLUSIONS: Abarelix as monotherapy achieves medical castration significantly more rapidly than combination therapy and avoids the testosterone surge characteristic of agonist therapy. Both treatments were equally effective in reducing serum prostate specific antigen, and achieving and maintaining castrate levels of testosterone.