An eight-month clinical study of LA-2575 30.0 mg: a new 4-month, subcutaneous delivery system for leuprolide acetate in the treatment of prostate cancer.

Objectives: To investigate the safety, efficacy, and pharmacokinetics of a new 4-month subcutaneous depot of leuprolide acetate in patients with prostate cancer.

Methods: Ninety patients diagnosed with adenocarcinoma of the prostate were enrolled in an open-label, multicenter study. LA-2575 30.0 mg was administered subcutaneously once every 4 months for 8 months. The primary efficacy parameter was a serum testosterone level of 50 ng/dL or less. The pharmacokinetics of leuprolide acetate were analyzed in the first 24 enrolled patients. The values are reported as the mean +/- standard error.

Results: Of 90 enrolled patients, 82 (91%) completed the 8-month study. Eight patients voluntarily withdrew from the study for the following reasons: nonmedical reasons (n = 3), treatment-related adverse events (n = 3), disease progression (n = 1), and cardiovascular disease (n = 1). By day 28, 85 (94%) of the 90 patients had achieved a serum testosterone level less than 50 ng/dL. At study completion, 88 (98%) of the 90 patients had a testosterone value less than the castrate level (mean 12.4 +/- 0.8 ng/dL), with 81 (90%) at less than 20 ng/dL. From baseline to month 6, the mean luteinizing hormone level had decreased from 7.51 +/- 0.69 mIU/mL to 0.12 +/- 0.02 mIU/mL. The mean prostate-specific antigen level had decreased 90% from 13.2 +/- 2.0 ng/mL at baseline to 1.3 +/- 0.3 ng/mL at 8 months. No clinically significant flare reactions were observed. The most common treatment-related adverse event was mild hot flashes.

Conclusions: LA-2575 30.0-mg depot consistently produced and maintained safe and effective suppression of serum testosterone, with total serum testosterone concentrations well below the medical castrate level of less than 50 ng/dL.