Phase III efficacy and safety trial of a new leuprolide acetate 3.75 mg depot formulation in prostate cancer patients

Abstract

e16152 Background: Androgen suppression is the standard palliative treatment for metastatic, localized or locally advanced prostate cancer. This phase III, open-label, international multicenter clinical study was conducted to investigate the efficacy and safety profile of a new formulation of leuprolide acetate (Lutrate 3.75mg Depot) in suppressing testosterone levels in prostate cancer patients. Methods: 160 patients with prostate cancer who could benefit from androgen deprivation therapy received single intramuscular injections of Lutrate 3.75 mg Depot every 28 days for a total of six doses. Plasma testosterone was determined at specific times throughout the study. The primary endpoint was the proportion of successful patients over the total number of evaluable patients. Patients’ success was defined as testosterone suppression (<0.5 ng/ml) at day 28 and continuance of castration until day 168, with no missing data at the monthly assessments. An exact two-sided binomial test (5% significance level) with two-sided 95% confidence interval (CI) estimated with exact method was performed to test the null hypothesis of 86% successful patients versus the alternative hypothesis of 94% . Results: The proportion of successful patients over the total number of evaluable patients was 96.8% (152/157); the exact binomial test was satisfied (p=0.000094, 90% CI: 92.7–99.0 %). The 78.7% (122/157) of evaluable patients achieved testosterone suppression by day 21. At day 28, 96.8% of the patients achieved castrate levels and 73.1% achieved testosterone levels ≤0.2 ng/ml. At conclusion of the trial, all patients (100%)maintained castration and 92.8% had testosterone levels ≤0.2 ng/ml. The most common treatment-related adverse event were hot flashes (45%), associated with testosterone suppression. Fatigue, hyperhydrosis, night sweats and headache occurred in ≤6.3% of patients. The most frequently reported local adverse reaction was pain at the injection site, experienced by 8.1% of patients. Conclusions: The results of this study demonstrate that Lutrate 3.75 mg Depot is as effective as presently marketed one-month leuprolide acetate formulations in establishing and maintaining testosterone concentration below castration levels in prostate cancer patients. [Table: see text]