Polymer-delivered, subcutaneously administered leuprolide acetate provides consistent and prolonged drug delivery in castrate men with advanced prostate cancer.

e586 Background: Leuprolide acetate (LA), a LHRH agonist, is standard of care in ADT in prostate cancer and used to suppress serum testosterone (T) to castrate level. Previously, in a head-to-head comparison of long-acting, polymer-delivered, subcutaneously administered LA (SC-LA) and microsphere intramuscularly administered LA depot (IM-LA) in healthy subjects, SC-LA demonstrated extended drug delivery compared to IM-LA, as well as prolonged T suppression. The objective of this study was to evaluate the safety and pharmacokinetics (PK) of SC-LA in orchiectomized, advanced prostate cancer patients to confirm and compare PK results with the head-to-head study. Methods: In this open label, single dose study, male, orchiectomized prostate cancer patients (ages 45-85) received a single dose of 7.5 mg SC-LA (labeled for 1 month dose interval). Blood samples were taken at baseline and at all scheduled visits up to day 56. LA concentration in serum was analyzed with HPLC. PK parameters AUC, Cmax, Tmax (time to Cmax), t 1/2 and concentration-time data were evaluated and adverse events (AEs) were assessed. Results: The study was conducted in 8 males with adenocarcinoma of the prostate (mean age = 72.5 y). Following administration, there was an initial rapid absorption phase with maximal concentrations observed at 2-6 hours. Serum LA fell slowly over 4-6 days and remained above 0.1ng/mL, the level associated with T suppression, for a mean of 37 days (range 28-49). Mean Cmax was 26.3 ±12.6 ng/mL with a mean Tmax of 3.79 ±1.39 h. AUC was 999 ±247 ng*h/mL. There were no serious treatment-related AEs and no subjects discontinued the study due to an AE. Conclusions: LA administered as a single, monthly SC dose via polymer delivery in orchiectomized prostate cancer patients showed extended drug delivery and T suppression 3 weeks past the dosing interval, mirroring extended PK in healthy subjects. Taken together, the PK profile of SC-LA demonstrates effective drug release throughout and beyond the labelled dosing interval.