Three-month depot of goserelin acetate: clinical efficacy and endocrine profile

Abstract

Objectives. To com pare the pharmacodynamics and tolerabiiity of the new goserelin acetate 10.8-mg depot with the 3.6-m g depot in patients with advanced prostate cancer during the first 3 months of therapy. Methods. One hundred sixty patients were randomized in two comparative studies to receive either the 10.8-m g goserelin acetate depot every 12 weeks or the 3.6-mg goserelin acetate depot every 4 weeks for 12 weeks and then the 10.8-m g depot every 12 weeks thereafter. Data for pharmacodynamic assessments were collected prospectively, whereas clinical response data were collected retrospectively. Results. Serum testosterone profiles of the 10.8-mg goserelin acetate depot and the 3.6-mg goserelin ac etate depot were sim ilar; testosterone levels in both groups fell below castrate levels by day 21 after ad ministration. D ecreases in serum prostate-specific antigen level after 3 months of therapy were also similar in both groups: 94% with the 10.8-m g depot and 9 2 .5 % with the 3.6-mg depot. For all patients, the median time to progression was 1 5 2 .7 weeks and the median time to death was 213.6 weeks. The safety profile of the 10.8-m g goserelin acetate depot was similar to that of the 3.6-mg depot; hot flashes was the most common adverse event. The incidence of injection site reactions was very low (2 [0.3% ] of 614 administra tions). Conclusions. The new 10.8-m g depot was pharmacodynamically equivalent to the current 3.6-mg depot and was well tolerated, both locally and system ically. The observed times to progression and survival were as expected in this patient population. The 10.8-mg gosereiin-acetate depot provided a dosing schedule that was convenient for the patient and the physician, and it has the potential to reduce health care costs while maintaining the quality of life in patients being treated for advanced prostate cancer.Copyright 1996 by Elsevier Science Inc. UROLOGY 48: 8 9 4 -9 0 0 , 1996. Since their in tro d u ctio n over a decade ago as a treatm en t for advanced prostate cancer, lu tein izing horm one-releasing horm one (LHRH) ago nist analogues have displaced estrogens as the leading alternative to orchiectom y for patients u n dergoing m o n o th e ra p y ,1 an d they have em erged as a co m p o n en t of com bination therapy w ith antian drogens in patients receiving com bined androgen

Leuprorelin Three-Month Depot in the Treatment of Advanced and Metastatic Prostate Cancer: Long-Term Follow-Up Results

“…Similar results have been obtained, with testosterone elevation observed in a minimal number of cases, after subcapsular orchiectomy [11,12], DES treatment [12] and after administration of goserelin 3-month depot [13]. As reported by the authors of this last study, the clinical condition of these patients was not impaired by the brief rise in serum testosterone.…”

“…The longer survival time with LAD-3M is primarily due to the fact that our study included patients with locally advanced carcinoma and was not confined to those with remote metastases. The retrospective data of del Moral et al [13] on goserelin 3M-depot report a similar time to tumor progression of 1,145 days compared to 1,015 days for LAD-3M. There are several possible reasons for the markedly longer median survival time of 1,495 versus 1149 days.…”

“…All 4 patients in our study were classified as having complete remission at the relevant final observation stage. It should be noted that a very strict definition of the castration range was applied in the present study: ^50 ng/dl or 1.73 nmol/l, while no definition of the upper limit of the castration range was given at all [14] or given as 2 nmol/l [13,15] or even as 100 ng/dl or 3.46 nmol/l [16], i.e. higher than our current definition by 15.7 or 100%.…”

Clinical significance of suboptimal hormonal levels in men with prostate cancer treated with LHRH agonists

“…This disparity in treatment selection is likely due to previous studies proving the efficacy of LHRH agonists, 5,6 the system of drug coverage in the Canadian health system and an unambiguous preference by patients to avoid what they perceive as a "mutilating" and esthetically undesirable procedure.…”

Controversies in the management of advanced prostate cancer

“…Goserelin acetate, leuprolide and triptorelin are all available as monthly intramuscular or subcutaneous injections. Goserelin acetate is now also available in a 12-weekly depot preparation for subcutaneous injection (Dijkman et al, 1995;Debruyne et al, 1996a), and leuprolide is also available as a 3-month depot in some countries (Fernandez Del Moral et al, 1996). These controlled-release preparations have obvious advantages in terms of patient compliance and acceptability.…”