Abstract
For more than 30 years, androgen-deprivation therapy (ADT) has been a standard treatment for advanced prostate cancer (PCa). This modality of treatment frequently utilises synthetic luteinising hormone-releasing hormone (LHRH) agonists such as leuprolide, goserelin, triptorelin, and buserelin, which are available as 1-, 2-, 3-, or 6-mo intramuscular or subcutaneous depot injections. A deep subcutaneous LHRH antagonist, degarelix, is also available but only as a 1-mo formulation. Despite their long track record of use, many current depot formulations of LHRH agonists have several disadvantages, including repeated administration, variable depot biodegradability, difficulty in removal, and variable duration of activity. The development and formulation of the most potent synthetic LHRH agonist, histrelin acetate, as a once-yearly subcutaneous implant (Vantas) that can be quickly and simply inserted superficially into the upper arm has provided several advantages over other currently available LHRH agonists. Histrelin acetate has been shown to quickly and effectively suppress serum testosterone levels to well below castrate level within 4 wk of treatment. This reduction in serum testosterone is paralleled with reductions in prostate-specific antigen and luteinising hormone. Importantly, when the histrelin implant is removed and a fresh implant is inserted, the efficacy has been shown to be extended up to 4.5 yr (with multiple reinsertions). In addition, the testosterone “surge” that is associated with the repeat administration of other currently available depot LHRH agonist formulations has been shown to be absent with the histrelin implant. A further benefit of the histrelin implant is the ease of removal and the rapidity with which the hypothalamic–pituitary–testicular axis may potentially normalise. Taken collectively, the properties of the histrelin implant offer potent and consistent suppression of serum testosterone with the benefit of easy and flexible administration.
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