Eligard ®: Pharmacokinetics, Effect on Testosterone and PSA Levels and Tolerability

Abstract

Luteinising hormone releasing hormone (LHRH) agonists (e.g. leuprolide) have been the mainstay of advanced and metastatic prostate cancer treatment. LHRH agonist treatment has also become part of the treatment of early prostate cancer as neoadjuvant and adjuvant treatment to radical therapy. Early therapies consisted of daily injections of synthetic LHRH analogues (e.g. leuprolide, goserelin), but recent years have seen the development of depot formulations with 1, 3 or 4-monthly injections. These depot formulations have contributed considerably to the current widespread use of LHRH agonists, and have improved the patients’ adherence to treatment. Unfortunately, with these formulations the achievement of optimal control of testosterone defined as appropriate castration levels and low levels of breakthroughs, as well as acute-on-chronic responses, is currently overestimated. In order to achieve the optimal control of testosterone, a new depot formulation of leuprolide, Eligard ®, has been developed, which contains a novel delivery system (Atrigel ®) with potential advantages over the older systems. Eligard ® allows for a favourable pharmacokinetic profile, delivering a twofold higher quantity of LHRH agonist than seen with other available depot preparations in the European Union (EU), in a consistent and stable manner. As a result, testosterone levels are better suppressed and, unlike other delivery systems, Eligard ® achieves levels of testosterone as seen with orchiectomy and has, to date, shown no escape responses. In addition, clinical trials have shown that Eligard ® produces mild episodes of hot flushes. Eligard ® has a small volume which is administered subcutaneously with a very short needle, reducing injection site discomfort. Main adverse events associated with subcutaneous injection are mild and of short duration, comprising irritation, skin discolouration and erythema. It is concluded that Eligard ®, consisting of a novel delivery system with an improved pharmacokinetic profile compared with other existing depot formulations, leads to reliable and sustained testosterone suppression with a favourable side effect profile.