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BJU Int. 2017 Feb;119(2):239-244. doi: 10.1111/bju.13482. Epub 2016 Apr 16.

Polymer-delivered subcutaneous leuprolide acetate formulations achieve and maintain castrate concentrations of testosterone in four open-label studies in patients with advanced prostate cancer.

Author information

1
Carolina Urologic Research Center, Myrtle Beach, SC, USA.
2
San Bernardino Urological Associates, San Bernardino, CA, USA.
3
Division of Urology, Department of Surgery and Duke Cancer Institute, Duke University, Durham, NC, USA.
4
Urology San Antonio, San Antonio, TX, USA.
5
Urology Associates, P.C., Nashville, TN, USA.
6
Tolmar, Inc., Fort Collins, CO, USA.
7
Tolmar Pharmaceuticals, Inc., Lincolnshire, IL, USA.
8
University of Colorado, Denver, Aurora, CO, USA.

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.

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 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.

KEYWORDS:

leuprolide acetate; luteinising hormone-releasing hormone agonist; prostate cancer; testosterone

PMID:
26991743
DOI:
10.1111/bju.13482
[Indexed for MEDLINE]
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