title: Polymer-delivered subcutaneous leuprolide acetate formulations achieve and maintain castrate concentrations of testosterone in four open-label studies in patients with advanced prostate cancer.
abstract: OBJECTIVE
  To determine whether luteinising hormone-releasing hormone (LHRH) agonist, ATRIGEL®polymer-delivered, subcutaneous, leuprolide acetate (ADSC-LA), formulations suppressed serum testosterone to concentrations of ≤20 ng/dL.
  
  
  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 androgen-deprivation therapy (ADT), were treated with a depot formulation of ADSC-LA: 7.5 mg (1-month, 120 patients), 22.5 mg (3-month, 117 patients), 30 mg (4-month, 90 patients), or 45 mg (6-month, 111 patients). Serum testosterone was sampled at screening, baseline, 2, 4, 8 h after dosing, 1, 2, 3, and 7 days, and every week until the next dose, at which time, the sampling schedule repeated until the end of study (24 weeks for 1- and 3-month formulations, 32 weeks for 4-month, and 48 weeks for the 6-month). The primary analyses were mean serum testosterone concentrations and proportion of patients who achieved concentrations of ≤20 ng/dL.
  
  
  RESULTS
  The mean (SE) serum testosterone concentrations at the end of study were consistently ≤20 ng/dL in each study, at 6.1 (0.4), 10.1 (0.7), 12.4 (0.8), and 12.6 (2.1) ng/dL for the 1-, 3-, 4-, and 6-month formulations, respectively. A high proportion of patients (94%, 90%, 92%, 96% for the 1-, 3-, 4-, and 6-month formulations, respectively) achieved testosterone concentrations of ≤20 ng/dL within 6 weeks, and 90-97% of patients in all studies maintained concentrations of ≤20 ng/dL from weeks 6-24.
  
  
  CONCLUSIONS
  Recent studies have shown improved outcomes in patients with prostate cancer who consistently attained a more rigorous level of testosterone suppression (≤20 ng/dL) with 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 concentration of ≤20 ng/dL. These data suggest that ADSC-LA delivers equivalent testosterone suppression as achieved by surgical castration.
authors.affiliation: Carolina Urologic Research Center, Myrtle Beach, SC, USA.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Shore
authors.affiliation: San Bernardino Urological Associates, San Bernardino, CA, USA.
authors.forename: Franklin
authors.initials: F
authors.lastname: Chu
authors.affiliation: Division of Urology, Department of Surgery and Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: Judd
authors.initials: J
authors.lastname: Moul
authors.affiliation: Urology San Antonio, San Antonio, TX, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Saltzstein
authors.affiliation: Urology Associates, P.C., Nashville, TN, USA.
authors.forename: Raoul
authors.initials: R
authors.lastname: Concepcion
authors.affiliation: Tolmar, Inc., Fort Collins, CO, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: McLane
authors.affiliation: Tolmar Pharmaceuticals, Inc., Lincolnshire, IL, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Atkinson
authors.affiliation: Tolmar Pharmaceuticals, Inc., Lincolnshire, IL, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Yang
authors.affiliation: University of Colorado, Denver, Aurora, CO, USA.
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D007279:Injections, Subcutaneous; D016729:Leuprolide / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011108:Polymers; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D013739:Testosterone / Q000097:blood*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011108:Polymers; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D016729:Leuprolide
keywords: leuprolide acetate; luteinising hormone-releasing hormone agonist; prostate cancer; testosterone