Serum testosterone suppression and potential for agonistic stimulation during chronic treatment with monthly and 3-month depot formulations of leuprolide acetate for advanced prostate cancer

Purpose: The pattern of serum testosterone suppression as well as the potential for agonistic stimulation of serum testosterone during chronic treatment was compared in patients with prostate cancer randomized to receive 4 depot injections of either the monthly or 3-month depot formulations of leuprolide acetate in an open label study. Materials and Methods: A total of 71 patients were enrolled in a randomized prospective study comparing the pattern of serum testosterone suppression and the potential for agonistic stimulation of serum testosterone following reinjection ("acute-on-chronic" effect) during treatment of advanced stage prostate cancer with monthly (7.5 mg.) and 3-month (22.5 mg.) depot formulations of leuprolide acetate. Results: The 2 formulations produced nearly identical patterns of testosterone suppression which included uniform suppression throughout the duration of the dosing intervals. A transient minor "escape" from suppression (defined as a single testosterone value greater than 50 ng./dl. once suppression was achieved) occurred in 1 patient receiving each formulation. Assessment of agonistic stimulation ("acute-on-chronic" response) following the second depot injection as well as the depot injection following 3 months of treatment for each formulation revealed no pattern of stimulation. Conclusions: We conclude that monthly and 3-month sustained release (depot) formulations of leuprolide acetate provide consistent, uniform suppression of serum testosterone throughout the respective dosing intervals, and that the initial depot injection of each formulation provides sufficient pituitary desensitization to prevent agnostic stimulation of serum testosterone during chronic treatment.