ATRIGEL(®) polymer-delivered subcutaneous leuprolide acetate formulations achieve and maintain castrate levels of testosterone in four open label studies in advanced prostate cancer patients.

OBJECTIVE - To determine whether an LHRH agonist, ATRIGEL(®) polymer-delivered, subcutaneous, leuprolide acetate (ADSC-LA) formulations suppressed testosterone to levels ≤20 ng/dL.

SUBJECT/PATIENTS AND METHODS - Data from four open-label, fixed-dose studies were evaluated.

Male patients aged 40-86 years with advanced prostatic adenocarcinoma, whom had not undergone prior ADT, were treated with a depot formulation of ADSC-LA: 7.5 mg [1 month (1M); N=120], 22.5 mg [3 months (3M); N=117], 30 mg [4 months (4M); N=90], or 45 mg [6 months (6M); N=111]. Serum testosterone was sampled at screening, baseline, 2, 4, 8 hours post-dosing, days 1, 2, 3, 7, and every week until the next dose, at which time, the sampling schedule repeated until the end of study (24 weeks for 1M and 3M, 32 weeks for 4M, and 48 weeks for the 6M dose). The primary analyses were mean serum testosterone levels and proportion of patients who achieved serum testosterone levels ≤20 ng/dL.

RESULTS - Mean serum testosterone levels at the end of study were consistently ≤20 ng/dL in each study (6.1±0.4, 10.1±0.7, 12.4±0.8, 12.6±2.1 for the 1M, 3M, 4M, and 6M doses, respectively). A high proportion of patients (94%, 90%, 92%, 96% for 1M, 3M, 4M, and 6M doses, respectively) achieved testosterone levels ≤20 ng/dL within 6 weeks, and 90-97% of patients in all studies maintained testosterone ≤20 ng/dL from weeks 6-24.

CONCLUSIONS - Recent studies have demonstrated improved outcomes in prostate cancer patients who consistently attained a more rigorous level of testosterone suppression (≤20 ng/dL) with androgen deprivation therapy (ADT) than the historical standard (≤50 ng/dL). All doses of ADSC-LA rapidly achieved and maintained mean serum testosterone to the more rigorous target level of T ≤20 ng/dL. These data suggest that ADSC-LA delivers equivalent testosterone suppression as achieved by surgical castration. This article is protected by copyright. All rights reserved.

BJU international. 2016 Mar 17 [Epub ahead of print]

Neal D Shore, Franklin Chu, Judd Moul, Daniel Saltzstein, Raoul Concepcion, John A McLane, Stuart Atkinson, Alex Yang, E David Crawford

Carolina Urologic Research Center, Myrtle Beach, SC, USA., San Bernardino Urological Associates, San Bernardino, CA, USA., Division of Urology, Department of Surgery and Duke Cancer Institute, Duke University, Durham, NC., Urology San Antonio, San Antonio, TX, USA., Urology Associates, P.C, Nashville, TN, USA., Tolmar, Inc, Fort Collins, CO, USA., Tolmar Pharmaceuticals, Inc, Lincolnshire, IL, USA., Tolmar Pharmaceuticals, Inc, Lincolnshire, IL, USA., University of Colorado Denver, Aurora, CO, USA.