9 The LA gel depot showed a longer duration of drug delivery and testosterone suppression compared to IM-LA. While IM-LA had a higher initial release and shorter Tmax (time to peak concentration), testosterone levels began to rise by day 42 in IM-LA patients, whereas the LA gel depot maintained suppression for over 50 days in most patients. The LA gel depot demonstrated more consistent and prolonged testosterone suppression, making it a more effective option for advanced prostate cancer treatment. 3.2.2.7. Evaluation of Late Dosing on Testosterone Suppression with LA Gel Depot and Microsphere Formulations This study analysed the impact of late dosing on testosterone suppression in prostate cancer patients treated with LA gel depot and LA microsphere (LA-MS) formulations. Late dosing was dened using two criteria: a "28-day month" and an "extended month." Results showed that late injections were common for both formulations, but the LA-MS treatment had higher rates of testosterone breakthroughs compared to the LA gel depot. For late injections, LA-MS was 1.5 times more likely to result in testosterone levels above 50 ng/dL or 20 ng/dL. The LA gel depot demonstrated better testosterone suppression consistency, even with delayed dosing, highlighting its effectiveness and reliability in maintaining therapeutic outcomes. 3.2.2.8. Evaluation of Intermittent vs Continuous Androgen Deprivation Therapy (ADT) The ICELAND study compared intermittent androgen deprivation (IAD) and continuous androgen deprivation (CAD) in patients with non-metastatic relapsing or locally advanced prostate cancer. Both regimens showed similar efcacy, tolerability, and quality of life outcomes. A post-hoc analysis further examined the correlation between testosterone levels during the rst year of CAD and survival outcomes. Patients were stratied into three groups based on testosterone levels: minimum (≤20 ng/dL), median (>20 to ≤50 ng/dL), and maximum (>50 ng/dL). All groups demonstrated comparable causespecic survival rates and time to PSA progression, indicating that CAD effectively lowers testosterone levels and maintains clinical benets regardless of the subgroup. 3.3. Safety of LA Gel Depot The LA gel depot is well-tolerated, with mild to moderate adverse events such as hot ushes and injection site reactions. It is contraindicated in patients with spinal metastases, spinal cord injury, and hypersensitivity to leuprorelin. 4. Expert Opinion The attributes for a perfect ADT are a sustained release of the drug between two injections, a sufcient and rapid suppression of the serum testosterone level and the reduction of testosterone breakthroughs. The leuprorelin acetate gel depot provides an advanced delivery method for advanced PCa due to its sustained testosterone suppression, minimal breakthroughs, and favourable safety prole. The 6-month formulation is associated with half the risk for patients to lose therapeutic effect due to delayed injection and thus provides improved patient compliance and quality of life by reducing injection frequency. It is a reliable backbone therapy for systemic treatment in metastatic hormone-sensitive and castration-resistant PCa. 5. Conclusion ADT remains the backbone therapy of advanced PCa. Among different options, longacting LHRH agonists represent the gold standard and the most used worldwide form of ADT. The leuprolide LA gel depot represents a second-generation LA formulation developed to ensure a controlled and sustained release of leuprorelin between injections and to reach lower castrate testosterone levels compared to other LHRH agonists.
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