A 12-Month Clinical Study of LA-2585 (45.0 MG): A New 6-Month Subcutaneous Delivery System for Leuprolide Acetate for the Treatment of Prostate Cancer

Crawford, E. David; Sartor, Oliver; Chu, Franklin; Perez, Ramon; Karlin, Gary; Garrett, J. Steve

doi:10.1016/S0022-5347(05)00161-8

« Previous Next »The Journal of Urology
Volume 175, Issue 2 , Pages 533-536, February 2006

A 12-Month Clinical Study of LA-2585 (45.0 MG): A New 6-Month Subcutaneous Delivery System for Leuprolide Acetate for the Treatment of Prostate Cancer

E. David Crawford
- University of Colorado Health Sciences Center, Fort Collins, Colorado
- Correspondence: Section of Urologic Oncology, University of Colorado Health Sciences Center, P. O. Box 6510, Mail Stop F-710, Aurora, Colorado 80045 (telephone: 720-848-0195; FAX: 720-848-0203)
- Financial interest and/or other relationship with Merck, Sanofi-Aventis, Celgene, Andrx/Auxilium, National Institutes of Health, University of Colorado Cancer Center, Oncura and Praecus.
Oliver Sartor
- Louisiana State University, New Orleans, Louisiana
- Financial interest and/or other relationship with Atrix Laboratories and Sanofi-Aventis.
Franklin Chu
- San Bernardino Urological Associates, San Bernardino, California
Ramon Perez
- Urology Health Center, New Port Richey, Florida
- Financial interest and/or other relationship with Atrix Laboratories and Sanofi-Aventis.
Gary Karlin
- Lawrenceville Urology, Lawrenceville, New Jersey
- Financial interest and/or other relationship with Atrix Laboratories.
J. Steve Garrett
- Aurora and Atrix Laboratories, Inc., Fort Collins, Colorado
- Financial interest and/or other relationship with QLT USA.

Received 8 March 2005

Purpose

The safety, efficacy and pharmacokinetics of LA-2585, a new 6-month subcutaneous depot of leuprolide acetate (Atrix Laboratories, Fort Collins, Colorado) were investigated in patients with prostate cancer.

Materials and Methods

In this 12-month, open label, multicenter study 111 patients with adenocarcinoma of the prostate were administered 45.0 mg LA-2585 subcutaneously once every 6 months. The primary efficacy parameter was serum testosterone 50 ng/dl or less. Leuprolide acetate pharmacokinetics were analyzed in a subset of 28 patients.

Results

Of the 111 enrolled patients 103 (93%) completed the 12-month study. Eight patients withdrew due to nonmedical reasons in 1, disease progression in 5 and cardiovascular disease in 2. By day 28, 108 of the 109 remaining patients (99%) achieved testosterone suppression, while 1 who never attained suppression was withdrawn at day 85. Mean time to castrate suppression was 21.2 days (median 21). At study completion 102 of 103 patients (99%) were below medical castrate testosterone levels of 50 ng/dl (mean ± SE 12.3 ± 2.1 ng/dl) with 91 of 103 (88%) at less than 20 ng/dl. Mean luteinizing hormone decreased from 6.98 ± 0.48 mIU/ml at baseline to 0.23 ± 0.14 mIU/ml at month 12. Luteinizing hormone was consistently below 1 mIU/ml. Mean prostate specific antigen decreased 97% from 39.8 ± 21.5 ng/ml at baseline to 1.2 ± 0.3 ng/ml at 12 months. No clinically significant flare reactions were observed. The most common treatment related adverse event was mild to moderate hot flashes.

Conclusions

LA-2585 (45.0 mg depot) consistently produced and maintained safe and effective serum testosterone suppression with total serum testosterone well below the medical castrate level of less than 50 ng/dl.

Key Words: prostate , clinical trials , prostate cancer , leuprolide , prostate-specific antigen

Abbreviations and Acronyms: C_max, maximum concentration , LA, leuprolide acetate , LH, luteinizing hormone , LHRH, luteinizing hormone-releasing hormone , PK, pharmacokinetic , PSA, prostate specific antigen