Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer.

PURPOSE: Zoledronic acid (ZA) or denosumab treatment reduces skeletal-related events; however, the safety of prolonged therapy has not been adequately studied. Here, we describe safety results of extended denosumab therapy in patients with bone metastases from the open-label extension phase of two phase 3 trials. METHODS: Patients with metastatic breast or prostate cancer received subcutaneous denosumab 120 mg Q4W or intravenous ZA 4 mg Q4W in a double-blinded fashion. Denosumab demonstrated superior efficacy in the blinded treatment phase; thus, patients were offered open-label denosumab for up to an additional 2 years. RESULTS: Cumulative median (Q1, Q3) denosumab exposure was 19.1 (9.2, 32.2) months in the breast cancer trial (n = 1019) and 12.0 (5.6, 21.3) months in the prostate cancer trial (n = 942); 295 patients received denosumab for >3 years. No new safety signals were identified during the open-label phase, or among patients who switched from ZA to denosumab. During the blinded treatment phase, exposure-adjusted subject incidences of osteonecrosis of the jaw (ONJ) were 49 (1.9%) and 31 (1.2%) in the denosumab and ZA groups, respectively. In total, 32 (6.9%) and 25 (5.5 %) new cases of ONJ (not adjusted for exposure) were reported for patients continuing and switching to denosumab, respectively. The incidences of hypocalcemia were 4.3 and 3.1%, in patients continuing and switching to denosumab, respectively. CONCLUSION: These results describe the safety profile of denosumab after long-term exposure, or after switching to denosumab from ZA. No new safety signals were identified. Hypocalcemia rates were similar in the blinded treatment and open-label phases. ONJ rates increased with increasing exposure to antiresorptives, consistent with previous reports.

Recreational ketamine use can lead to irreversible bladder damage.

An increasing number of young patients with severe bladder overactivity syndrome potentially caused by recreational ketamine use has been treated in our department. Ketamine has become a popular and increasingly used recreational drug in New Zealand. Ketamine bladder syndrome has been reported internationally; however, local New Zealand data do not exist. It can lead to irreversible damage to the bladder, and internationally, surgical procedures like cystectomy and urinary diversion or augmentation cystoplasty have been reported as necessary treatments.

Cystoprostatectomy versus prostatectomy alone for locally advanced or recurrent pelvic cancer.

BACKGROUND: There is minimal published data evaluating the oncological outcome of rectal resection with prostatectomy alone versus rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer. This study aims to evaluate the oncological and functional outcomes of performing rectal resection with prostatectomy alone compared with rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration. METHODS: Consecutive patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer between 1998 and 2012 were identified from a prospectively maintained database. Patients undergoing rectal resection with prostatectomy alone were compared with a control group who underwent rectal resection with cystoprostatectomy and urostomy formation. The primary outcome was overall survival. Secondary outcomes analysed in the prostatectomy group included completeness of resection, continence and erectile function. RESULTS: Eleven rectal resections with prostatectomy were compared with 20 rectal resections with cystoprostatectomy. R0 resection was achieved in 73 and 65% respectively. There was no difference in overall survival (P = 0.40). Urinary continence was achieved in 36% of prostatectomy alone patients, while 27% experienced mild incontinence. Erectile function was poor, with only one patient able to maintain normal erections. CONCLUSION: In appropriately selected patients with invasive pelvic tumours, rectal resection with prostatectomy alone provides adequate oncological outcomes. The ability to achieve an R0 resection was not compromised and overall survival is comparable with cystoprostatectomy. Urinary function is reasonable in most patients, although sexual function is compromised in almost all.