Serum testosterone-based luteinizing hormone-releasing hormone agonist redosing schedule for chronic androgen ablation: A phase I assessment

Objectives. To assess the potential for using the serum testosterone level as the guide for redosing depot luteinizing hormone-releasing hormone (LHRH) agonist and to characterize the duration of castrate level testosterone after the last 22.5-mg leuprolide injection repeatedly administered for the control of prostate cancer. Methods. Informed consent was obtained from 32 men with prostate cancer (Stage T3N+/- M+/- or greater) treated with 3-month (22.5-mg) leuprolide acetate injection. Serum testosterone and prostate-specific antigen levels were obtained every 28 days beginning on the 90th day after the last 22.5-mg leuprolide injection. The duration of action was the calculated interval, in months, between the last injection and the first noncastrate serum testosterone (greater than 0.2 ng/mL) value. Results. The median duration of castrate level testosterone was 6.0 months (SE +/- 0.15; upper and lower quartile 5.3 and 7.0, respectively). Prostate cancer biochemical (prostate-specific antigen) activity at enrollment and when the castrate testosterone threshold of 0.2 ng/mL was exceeded remained stable, with no significant change observed during this interval (P = 0.52). A significant association was observed between an increasing duration of castration after LHRH agonist injection and advancing patient age (P = 0.03) and increasing duration of hormonal therapy (P = 0.05). Conclusions. These results suggest that using the serum testosterone level to guide in redosing of long-acting LHRH agonist may provide a novel, effective, and economical method to administer hormonal ablative therapy in patients with prostate cancer. These observations have important implications for product dosing and the design and interpretation of neoadjuvant and intermittent androgen ablative trials. Published by Elsevier Science Inc.