4609 Background: Ipilimumab is a fully human anti-CTLA-4 IgG1 monoclonal antibody that blocks CTLA-4 and augments immune responses. The current study evaluated the safety and activity of ipilimumab alone or with a single dose of docetaxel in hormone-refractory prostate cancer (HRPC). Methods: 43 chemotherapy naïve patients (pts) with HRPC, were treated; 23 were in arm A (ipilimumab at 3 mg/kg q 4 weeks × 4 doses) and 20 in arm B (ipilimumab as in Arm A and one dose of 75 mg/m2 of docetaxel on day 1). Results: Six pts, 3 in each arm, demonstrated a decrease in PSA of > 50%. Three pts, 2 in arm A, and 1 in arm B had confirmed PSA responses with durations of 79+ days, 169+ days, and 280 days, respectively. There were no radiologic responses with these PSA responses. Thirty-six (84%) of the 43 pts experienced 1 or more adverse events considered to be related to treatment with ipilimumab. The most common adverse events included fatigue (44%), pruritus (26%), nausea (19%), rash (12%), constipation (12%), and weight loss (12%). Serious adverse events (SAEs) occurred in 18 patients (42%), who experienced 52 SAEs. The majority (42 out of 52, 81%) were judged by the Investigator to be unrelated or unlikely to be related to treatment with ipilimumab. Five of the 52 SAEs reported in 3 pts were considered to be possible immune breakthrough events (IBEs), associated with drug exposure and consistent with an immune-based mechanism of action. These were adrenal insufficiency (1), diarrhea, colitis, and melena (all in one patient) and colitis (1). One of these pts had a confirmed PSA response. Conclusions: Ipilimumab was well tolerated in this group of pts with HRPC. Three pts overall (6%) experienced an IBE, a phenomenon that has been correlated in other studies with efficacy. There were several confirmed responses as assessed by PSA, one of which was correlated with an IBE. There was no apparent enhancement of activity by coadministration of a single dose of docetaxel. Further studies exploring ipilimumab in prostate cancer are warranted, either as monotherapy at higher doses, or in combination with immune modulators or vaccines. [Table: see text]
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Modern cryoablation of the prostate is a procedure that has evolved since the early 1990s into a safer and more successful treatment of adenocarcinoma of the prostate. The improvement of this technique has taken place secondary to advancement in engineering, procedure refinement, temperature monitoring, and a better understanding of physiologic events during the freezing process. Long-term results are available that demonstrate durable efficacy equivalent to other therapies in low-risk groups. In moderate to high risk groups, results point toward equal to superior results than other standard therapies. New ideas on potency preservation using vacuum erection devices have improved men's return to function over the course of the postoperative year. Early morbidity issues, such as fistula formation and incontinence, have become much less problematic, with results between 0% and 1% in some series. Cryoablation of the prostate now offers significantly improved outcomes with a parallel decrease in morbidity.
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