Is High-Dose Leuprorelin Acetate Effective and Safe in Asian Men with Prostate Cancer? An Open-Label, Non-Comparative, Multi-Center Clinical Trial

Abstract

PurposeLeuprorelin is a well known luteinizing hormone releasing hormone agonist. However, there are insufficient data on the efficacy and safety of high dose leuprorelin acetate, especially in Asian patients with prostate cancer. We aimed to investigate the safety and efficacy of leuprorelin acetate 22.5 mg administered at three-month intervals in patients with prostate cancer.Materials and MethodsIn an open, prospective clinical trial enrolling 47 patients, we aimed to assess the efficacy and safety of leuprorelin acetate 22.5 mg in treating patients with histologically confirmed prostate cancer. The primary objective of this study was to evaluate the efficacy of the leuprorelin acetate 22.5 mg in producing and maintaining castration levels of testosterone over a 6-month follow-up period and to determine its safety profile.ResultsAll 42 patients achieved serum testosterone levels within the castration range by 4 weeks. A breakthrough response was observed in one of 36 patients by 8 weeks. However, this patient was medically castrated by 12 weeks. There were no significant prostate-specific antigen (PSA) or testosterone changes according to clinical stage or body mass index. Twenty adverse events (AEs) in 15 of 42 patients (35.7%) were observed during this study. The most common AEs were hot flushes (n=4, 20.0%) with mild intensity, pain (n=2, 10.0%), and infection (n=2, 10.0%). No patient withdrew from the study due to AEs.ConclusionLeuprorelin acetate 22.5 mg was shown to be effective and safe in Asian patients with prostate cancer, even though sexual function decreased.

ELIGANT: a Phase 4, interventional, safety study of leuprorelin acetate (ELIGARD®) in Asian men with prostate cancer

“…Overall, the safety profile was consistent with previous trials of 22.5 mg ELIGARD ® in Europe, Asia, and the United States, with no new safety signals reported (18,19,26,27). In these trials, the most common TEAEs reported included hot flush, hypertension, and constipation in the European ICELAND study; hot flush, fatigue, and nausea in the United States; and hot flush, pain, and infection in Asian men with prostate cancer (18,19,26,27). In particular, the Phase 3 ICELAND study, which enrolled 933 men across Europe, reported both a similar frequency of TEAEs overall (72.5% vs. 75.5% for ELIGANT) and a comparable proportion of TEAEs with grade ≥3 severity (27.3% vs. 35.9%) with 22.5 mg ELIGARD ® in prostate cancer (19).…”

“…These events are frequently observed with many ADT treatment options, including LHRH agonists goserelin and triptorelin (24,25). Overall, the safety profile was consistent with previous trials of 22.5 mg ELIGARD ® in Europe, Asia, and the United States, with no new safety signals reported (18,19,26,27). In these trials, the most common TEAEs reported included hot flush, hypertension, and constipation in the European ICELAND study; hot flush, fatigue, and nausea in the United States; and hot flush, pain, and infection in Asian men with prostate cancer (18,19,26,27).…”

A Semi-Mechanistic Integrated Pharmacokinetic/Pharmacodynamic Model of the Testosterone Effects of the Gonadotropin-Releasing Hormone Agonist Leuprolide in Prostate Cancer Patients

“…In one study conducted in 49 prostate cancer patients, it was observed that men with a BMI [30 kg/m 2 had higher total and free testosterone levels during leuprolide 3-month depot treatment than men with a normal BMI [33]. Other studies, however, have not noted differences in serum testosterone concentration among normal weight, overweight, and obese patients receiving GnRH agonist therapy for prostate cancer [34][35][36]. Furthermore, in the larger pivotal clinical study of the 6-month depot formulation (n = 150) [14], it was observed that serum testosterone was suppressed to values B0.5 ng/mL from week 4 through week 48 at a similar rate for the subgroups based on BMI.…”

Sequencing of Systemic Therapies in the Management of Advanced Prostate Cancer in India: a Delphi-Based Consensus

“…Although available ADT provides similar efficacy, evidence suggests that degarelix provides both cardiovascular and oncologic benefits, in contrast to GnRH agonist therapy [25]. Also, a study has reported the safety and effectiveness of leuprolide in the Asian population of prostate cancer patients, albeit in association with decreased sexual function [26].…”