ANAHEIM, CA (UroToday.com) - This session discussed the growing understanding of side effects associated with androgen blockade therapy as well as some novel therapies for this condition. In regard for the latter, Yap and colleagues described a phase I trial of abiraterone acetate, an oral irreversible inhibitor of CYP 17 in patients with chemotherapy naive androgen independent prostate cancer [ABST 594]. 18 patients were studied at doses ranges from 250mg to 2000 mg daily. No dose limiting toxicity was noted. Revesible grade two hypertension was noted in 6 patients. Circulating testosterone levels were in the castrate range and then became undetectable in all patients. Of 12 evaluable patients 8 have PSA declines greater than 50% and 6 have greater than 90 % declines. By RECIST criterial 5 patients have had a radiological partial response. A phase II study has been started to further evaluate the feasibility of this agent as a second line hormonal therapy for this condition.

Several abstracts dealt with the complications of androgen blockade. Malcom and associates described the frequency of cerebrovascular accidents and myocardial infarction in patients with androgen deprivation therapy (ADT) [ABST 597]. An analysis of 395 patients of a mean age of 71 followed for an average of 66.1 months. 4.6% of patients suffered an MI and 5.8% had a CVA and average of 49 and 64 months status post initiation of treatment. While these data are of concerned, further evaluation of control population matched cohorts will be necessary to better evaluate this situation. In a multinational study reported on by Gallina, The increased risk of new comorbidities in patients treated with ADT were described. In a cohort of 14,839 patients 38.5% were treated with ADT. Median patient age was 68. Using the Charlston comorbidity score, the baseline comorbidities were 2. ADT was associated with an increased risk of MI (HR 1.29, p<0.01), congestive heart failure (HR 1.24, p< 0.005, dementia (HR 1.54, p< 0.001) and moderate to severe renal insufficiency (HR 1.34, p = 0.004). This is reasonably strong evidence that ADT may predispose patients to adverse medical outcomes. Tunn reported on a randomized prospective trial of intermittent androgen blockade after radical prostatectomy biochemical failure [ABST 600]. 224 patients were evaluated and 167 were randomized to continuous androgen ablation or intermittent therapy. The mean age in both groups was approximately 67. The off treatment time was 368 days in the first cycle and 171 days in the second cycle. Treatment was reinstitued when PSA values rose above 3.0 ng/mg. The mean number of days with hot flashes during the study period of two years was 46 days in the continuous group and 23 days per quarter in the intermittent group. No differences were noted with respect to progression to androgen independent disease. This prospective study is promising in showing a lack of inferiority of intermittent blockade to continuous blockade and may provide very useful data with further maturity.

Petrylak reported on the impact of docetaxel on those patients who had received sipuleucel-T (APC8015) an investigational autologous active cellular immunotherapy [ABST 605]. An exploratory analysis was performed on those patients in the two studies who received docetaxel after primary treatment with sipuleucel-T. Survival analysis was performed on 82 patients and a 47% reduction in risk of death was relative to othose randomized to placebo was noted (HR 1.9, p=0.023). The median survival for the patients receiving sipuleucel-T was 34.5 months compared to 25.4 months for placebo. These data suggest the potential rationale for treatment with sipuleucel-T followed by docetaxel in patients with AIPC. Optimal dosage and timing would be best evaluated in future clinical trials.

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Written by S.Bruce Malkowicz, MD, a Contributing Editor with UroToday.

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