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 a fter 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 (St age T3N+/- M+/- or greater) treated with 3-month (22.5-mg) leuprolide aceta te injection. Serum testosterone and prostate-specific antigen levels were obtained every 28 days beginning on the 90th day after the last 22.5-mg leu prolide injection. The duration of action was the calculated interval, in m onths, between the last injection and the first noncastrate serum testoster one (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 = 0.0 3) 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, effec tive, and economical method to administer hormonal ablative therapy in pati ents with prostate cancer. These observations have important implications f or product dosing and the design and interpretation of neoadjuvant and inte rmittent androgen ablative trials. Published by Elsevier Science Inc.