6 Advanced delivery of leuprorelin acetate for the treatment of prostatic cancer A summary from the article by Axel S Merseburger & Marie Christine Roesch published in Expert Review of Anticancer Therapy 2022, Vol. 22, No. 7, 703 – 715. 1. Introduction Prostate cancer (PCa) is the most common cancer in Europe, with an increasing incidence projected from 2020 to 2030. Androgendeprivation therapy (ADT) is the cornerstone treatment for advanced and metastatic prostate cancer PCa, aiming to reduce serum testosterone levels to castration levels (<20 ng/dL) and thus inhibiting the growth of tumour cells. Luteinizing hormone-releasing hormone (LHRH) agonists and antagonists are widely used due to their effectiveness and tolerability. Due to its favourable tolerability, leuprorelin acetate (LA) is well established as one of the leading luteinizing hormone-releasing hormone (LHRH) analogues. A second-generation LA depot formulation has been developed to ensure a controlled and sustained release of leuprorelin between injections and to reduce testosterone levels more efciently compared to conventional LHRH agonists. 2. Leuprorelin Acetate for the Treatment of PCa: Biological and Clinical Rationale Leuprorelin acetate, a synthetic analog of gonadotropin-releasing hormone (GnRH), has been used for over 30 years to treat PCa. It effectively lowers testosterone levels, delays tumour progression, and alleviates symptoms like bone pain. Its tolerability and exibility of administration make it one of the leading LHRH analogs worldwide. 3. Advanced Delivery of Leuprorelin Acetate 3.1. LA Gel Depot Pharmacokinetics The LA gel depot formulation uses the Atrigel® delivery system to provide sustained testosterone suppression over 6 months (45 mg formulation) and is also available in 1- and 3month formulations (7.5 mg and 22.5 mg formulations). After injection, leuprorelin acetate levels rise initially and then stabilize at a constant level, ensuring no accumulation over long-term treatment. Editors note: the 1 month formulation is not currently available in South Africa 3.2. Therapeutic Activity of the LA Gel Depot The latest evidence suggests that a proper threshold for testosterone levels should be <20 ng/dL as the mean testosterone level achieved by surgical castration is 15 ng/dL. The LA gel depot achieves testosterone suppression below 20 ng/dL in most patients, with minimal testosterone breakthroughs. Clinical trials demonstrated its efcacy in reducing testosterone and PSA levels, with consistent results across all formulations. 3.2.1. Pivotal Trials Three pivotal trials conrmed the LA gel depot's ability to suppress testosterone levels to ≤20 ng/dL in 88–97% of patients, depending on the formulation. Minimal testosterone breakthroughs (<1%) were reported, and PSA levels decreased signicantly. This sustained and persistent testosterone suppression is of clinical relevance as testosterone ares are often associated with morbidity.
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