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.
OBJECTIVE
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.
Sartor
Oliver
O
Louisiana State University School of Medicine, New Orleans, Louisiana, USA.
Dineen
Martin K
MK
Perez-Marreno
Ramon
R
Chu
Franklin M
FM
Carron
Graham J
GJ
Tyler
Robert C
RC
D000368:Aged; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016729:Leuprolide / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D013739:Testosterone / Q000097:blood
D003692:Delayed-Action Preparations; D011108:Polymers; D011760:Pyrrolidinones; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013739:Testosterone; D016729:Leuprolide