Zoledronic acid combined with androgen-deprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naïve metastatic prostate cancer patients - A propensity scoring approach.

OBJECTIVE: To clarify the oncological benefit of zoledronic acid for hormone-naïve metastatic prostate cancer, patient outcome of androgen deprivation therapy with zoledronic acid (ADT + Z) and androgen deprivation therapy alone (ADT) was compared. METHODS: Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade (goserelin and bicalutamide) with zoledronic acid (4 mg every 4 weeks for 24 months). A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts (both from ADT + Z and from historical control cohorts who had undergone ADT alone), and patient outcomes were compared. RESULTS: Patients with ADT + Z had significantly longer time to progression (TTP) than those with ADT (median TTP; 24.2 vs. 14.0 months, p = 0.0092), while no significant difference of overall survival between two groups (p = 0.1502). Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor (HR: 1.724, 95% CI: 1.06-2.86, p = 0.0297). CONCLUSION: Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

Naftopidil versus flopropione as medical expulsive therapy for distal ureteral stones: results of a randomized, multicenter, double-blind, controlled trial.

PURPOSE: A multicenter, double-blind, randomized, controlled trial was conducted to determine the efficacy of naftopidil as medical expulsive therapy (MET) for patients with distal ureteral stones. METHODS: Ninety-two patients presenting with a single distal ureteral stone ≤10 mm were randomly assigned to receive either naftopidil (75 mg of naftopidil once in the morning and placebo twice a day) or flopropione (80 mg three times a day). The primary end point was time to stone expulsion calculated by the Kaplan-Meier method. Secondary end points were the percentages of patients who required analgesics, hospital admission, and surgery, the number of working days lost to the disease, and treatment safety. RESULTS: Overall, three patients were excluded from the final analysis. No significant differences were noted in age, stone size, and stone side between the treatment arms. The median time to stone expulsion was 8 days [95 % confidence interval (CI), 3-16] for the naftopidil group, and this was significantly less than the 18 days (95 % CI, 11 to not reached) for the flopropione group (p = 0.03). On multivariate Cox regression analysis, the hazard of expulsion was 1.8-fold higher for the naftopidil group than for the flopropione group after adjustment for age, sex, stone side, and stone size. No significant differences were noted in the secondary end points. CONCLUSIONS: The administration of naftopidil significantly improved time to stone expulsion in patients with distal ureteral stones ≤10 mm. We believe that this is the first multicenter, double-blind, randomized, controlled trial demonstrating the efficacy of naftopidil for MET.

Significance of baseline bone markers on disease progression and survival in hormone-sensitive prostate cancer with bone metastasis.

PURPOSE: This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer. METHODS: Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks. RESULTS: A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 µg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months. CONCLUSIONS: Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

Botulinum toxin A injection for the treatment of neurogenic detrusor overactivity secondary to spinal cord injury: multi-institutional experience in Japan.

OBJECTIVES: To examine the efficacy and safety of onabotulinumtoxinA (Botox) injection into the bladder wall for the treatment of neurogenic detrusor overactivity secondary to spinal cord injury in Japanese patients. METHODS: We enrolled Japanese spinal cord injury patients with cystometrically confirmed neurogenic detrusor overactivity who experienced urinary incontinence at least once a week either because they were refractory to anticholinergics or had to discontinue treatment because of adverse events. Patients received 200 units of onabotulinumtoxinA injected into the bladder wall after a 2-week washout of anticholinergics, and urodynamic variables were assessed before and 1 month after injection. Catheterization and urinary incontinence data, as well as International Consultation on Incontinence Questionnaire-Short Form scores, were assessed before injection and every month thereafter until the cessation of treatment effects. RESULTS: The study enrolled 19 patients (13 men, six women, age range 22-67 years). One month after injection, the mean number of urinary incontinence episodes decreased from 4.3 to 1.5 times/day (P = 0.004), and the maximum cystometric capacity increased from 100 mL to 296 mL (P = 0.0004). The rate of effective cases whose daily urinary incontinence frequency was decreased to less than 50% was 74%. The duration of efficacy without anticholinergic medication ranged from 3 to 12 months (median 8.5 months). Clinically significant adverse events were not observed. CONCLUSIONS: The present findings show the efficacy and tolerability of onabotulinumtoxinA injection for the treatment of neurogenic detrusor overactivity in Japanese spinal cord injury patients.

Phase II trial of zoledronic acid combined with androgen-deprivation therapy for treatment-naïve prostate cancer with bone metastasis.

BACKGROUND: The efficacy of zoledronic acid in patients with treatment-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-naïve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months. METHODS: Subjects were treatment-naïve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months. RESULTS: Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %). CONCLUSION: Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-naïve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.

Botulinum toxin A submucosal injection for refractory non-neurogenic overactive bladder: early outcomes.

The objective of the present study was to assess the short-term effects of botulinum toxin A (BTX-A) injection for refractory non-neurogenic overactive bladder (OAB) in the setting of a prospective multicenter clinical trial. Refractory OAB was defined as persistent urgency urinary incontinence (UUI) ≥ once a week despite taking anticholinergic agents, or the incapability to continue the agents because of the adverse effects. A total of 100 U of BTX-A were reconstituted in 15 mL of normal saline and an aliquot of 0.5 mL was injected at 30 submucosal sites of the bladder wall. Nine men and eight women aged 67 ± 12 years were included. Subjective daytime frequency, urgency and UUI significantly decreased after treatment. On a 3-day frequency-volume chart, the daytime and night-time frequency of UUI significantly decreased from 5.5 and 0.5 pre-injection to 2.0 and 0.3 postinjection, respectively. Daytime urinary incontinence completely disappeared in six subjects. A urodynamic study showed the disappearance of detrusor overactivity in eight patients and a decrease in five patients. Maximum bladder capacity significantly increased from 179.9 to 267.3 mL. Difficulty on micturition or feeling of incomplete emptying was reported by 23.5% and 43.8% of patients at weeks 2 and 4, respectively. Postvoid residual urine increased to >100 mL in seven patients and >200 mL in one patient after injection; however, none of the patients required clean intermittent catheterization. These findings suggest promising efficacy of BTX-A in Japanese OAB patients.