COMPARISON OF LH-RH ANALOG 1-MONTH DEPOT AND 3-MONTH DEPOT BY THEIR HORMONE LEVELS AND PHARMACOKINETIC PROFILE IN PATIENTS WITH ADVANCED PROSTATE-CANCER

In an open, randomized phase II pharmacokinetic study conducted in Ger many and Italy, a total of 42 patients with advanced or metastatic pro state cancer (PCa) were treated for 9 months with the luteinizing horm one-releasing hormone analogue (LH-RH-a) leuprorelin acetate depot in two different formulations. Fifteen patients received the 1-month depo t and 27 patients received the newly developed 3-month depot, containi ng 3.75 mg and 11.25 mg, respectively. In both groups, subcutaneous in jections of leuprorelin acetate injected monthly or at 3-month interva ls produced a complete down-regulation of the pituitary and led to per sistent suppression of testosterone and dihydrotestosterone to the cas trate range (less than or equal to 50 ng/dl for testosterone) within t he first month of treatment, which thereafter could be maintained over the entire observation period of 9 months. In 10 patients, pretreatme nt with an antiandrogen for the prevention of clinical flare-up result ed in a slightly more profound and earlier drop in serum testosterone. The 3-month depot showed a higher median peak serum concentration (C- max) of leuprorelin at 20.8 ng/ml than the 1-month depot at 10.7 ng/ml but, conversely, this did not influence the rise in serum testosteron e levels. C-max occurred at 3 h for the 3-month and at 1 h for the 1-m onth depot formulation. During the steady state, constant release coul d be detected, starting on day 3 and day 7 for the 1-month and 3-month depot, respectively. A marked decrease in median prostate-specific an tigen levels of 97.8% (1-month depot) and 96.6% (3-month depot) compar ed with baseline was observed, indicating an objective clinical respon se for more than 80% of all patients in both arms. Based on European O rganization for Research and Treatment of Cancer criteria, the best re sponse in terms of complete/partial remissions and stabilization was c omparable in the two arms at 86.7% (1-month depot) and 85.2% (3-month depot). 6.7% in the 1-month group and 3% in the 3-month depot group sh owed progression of the disease. The most common side effects in both treatment groups were related to hormone deprivation. Both formulation s of the potent LH-RH-a leuprorelin acetate were highly effective in t he treatment of advanced PCa and led to comparable endocrine and clini cal effects.