Late administration of luteinizing hormone-releasing hormone (LHRH) agonists and the impact on testosterone suppression in the real-world management of prostate cancer.

Abstract

149 Background: LHRH agonists are standard for androgen deprivation therapy (ADT) for advanced prostate cancer (PCa). Increasing evidence suggests maintaining very low testosterone (T) levels is desirable and correlate with disease-specific survival. However, T levels may rise above castrate level between administrations, especially if the next dose is delayed. A previous publication showed that subcutaneously-administered leuprolide acetate (LA) provided a longer duration of action than intramuscularly-administered LA past the dosing interval. This study evaluated the timeliness of LHRH agonist administrations and subsequent rate of T breakthroughs in PCa patients. Methods: A retrospective review of electronic medical records from 1/1/07-6/30/16 of 85,030 LHRH agonist administrations for PCa treatment was conducted to evaluate the percentage of late subsequent administrations and T tests with T > 50 ng/dL. A late administration was defined as occurring on or after day 33 (1 mo formulation), 98 (3 mo), 129 (4 mo), or 195 (6 mo). Descriptive statistics were used. Results: 26.9% of all subsequent LHRH agonist administrations were late: 14.4% were ≤ 1 week late, 3.1% were between 1 and 2 weeks late, and 9.4% were > 2 weeks late. 21% of T tests demonstrated T > 50 ng/dL when administrations were late, in contrast to only 4% of measured T levels exceeded 50 ng/dL when LHRH agonists were administered early or on time. Conclusions: Across LHRH agonists, greater than a quarter of subsequent administrations were defined as late. Among late administrations, about half were > 1 week late, and more than a third were > 2 weeks late. Late administrations were correlated with inadequate castration over 20% of the time. Considering the clinical benefits of maintaining effective T suppression during ADT, clinicians should administer treatments within approved dosing instructions, include routine monitoring of T levels, and consider prescribing treatments with proven prolonged effect through the dosing period to achieve T suppression to castrate levels.