Efficacy and Safety of Leuprorelin Acetate Depot for Prostate Cancer

Abstract

In an open, prospective clinical trial enrolling 205 patients, efficacy and safety of the gonadotropin-releasing hormone agonist leuprorelin acetate depot (LAD) in the treatment of patients with advanced prostatic carcinoma were assessed. 3.75 mg of the LAD formulation was injected subcutaneously in monthly intervals. The primary objective of this study was to evaluate the efficacy of the analogue in producing and maintaining castration levels of testosterone over a > 3-year follow-up period and to determine its safety profile. Median pretreatment serum testosterone levels fell from 350 to 21 ng/dl after 4 weeks and 20 ng/dl after 45 months. The long-term clinical efficacy of the LAD formulation can be expressed by best treatment response over time. These respective figures read as follows: 10.7% complete response; 49.8% partial response; 34.1% no change; 1.5% progression, and 3.9% no data available. The median time to progression was 12(15 ± 11) months. Median survival time calculated by Kaplan-Meier exceeded 42.5 months for patients on monotherapy and 30.9 months for those on combination therapy. Hot flushes which were related to androgen deprivation were the most common side effects. Patients and treating physicians judged tolerability of LAD in more than 90% as good. Androgen deprivation remains the mainstay of hormone-dependent advanced carcinoma of the prostate. Up to now, surgical castration has been considered the standard method. LAD is an advantage in the endocrine treatment of advanced prostatic carcinoma and is a good alternative to castration.

Comparison of LH-RH Analogue 1-Month Depot and 3-Month Depot by Their Hormone Levels and Pharmacokinetic Profile in Patients with Advanced Prostate Cancer

“…The kinetic data found in this study for the 1-month depot, e.g. C max and t max , are in concordance with previously published results [2].…”

“…The median PSA reduction achieved with the 1-month and 3-month depot was in a range similar to that reported in the literature for other LH-RH-a [9][10][11] or after bilateral orchiectomy [12]. The response rates obtained, which were virtually identical in the two arms, coincide with the results of previously published experience with both leuprorelin formulations [2,7,13].…”

“…Injectable monthly depots have greatly contributed to their widespread use and acceptance as well as to patient compliance [2]. It therefore seemed logical to develop even longer-acting depot formulations in order to tailor the treatment more to the individual patient's environment and quality of life.…”

Safety and clinical efficacy of a new 6-month depot formulation of leuprorelin acetate in patients with prostate cancer in Europe

“…These results are consistent with other study results published with the well-established 3M depot of leuprorelin acetate showing clinical response rates of 76, 72, 84 and 85%. 3,[6][7][8] Objective progression rate at any time point during the study was slightly higher, but not statistically significant, in the 6M depot group, which may be due to more advanced tumour stages in this group, that is more distant metastases, more lymph node involvement, higher tumour grade, higher Gleason Scores and longer time since first diagnosis. By final examination at month 12, more than 90% of patients in both groups showed no progression.…”

Evaluation of orntide microspheres in a rat animal model and correlation to in vitro release profiles

“…Leuprolide acetate, developed and marketed by TAP Pharmaceuticals, Inc. (Deerfield, Ill.) as Lupron Depot®, is one of the most widely used LHRH superagonists in the treatment of sex hormone-dependent tumors, such as prostatic carcinoma in men [5][6][7]. During continuous administration, Leuprolide initially stimulates production and release of testosterone, but the prolonged exposure to an LHRH superagonist eventually causes down-regulation of LHRH receptors and inhibition of luteinizing hormone (LH) release, which finally leads to chemical castration [8,9]. Due to this initial testosterone elevation, which may last in humans from 5 to 8 days, approximately 11% of all treated patients experience painful and potentially dangerous flare-ups of disease [10][11][12][13][14].…”