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Abstract
Background: A microencapsulated, sustained-release formulation of leuprolide acetate 3.75 mg
has been developed.
Objective: This study investigated the effectiveness, pharmacokinetics, and safety profile of
a 1-month leuprolide acetate 3.75-mg depot formulation for suppressing testosterone
concentrations in patients with prostate cancer.
Methods: This was a Phase III, open-label, international multicenter clinical trial. Patients
with prostate cancer who, in the judgment of the investigators, could benefit from
androgen deprivation therapy received 6 monthly intramuscular injections of leuprolide
acetate 3.75-mg depot. Plasma testosterone concentrations were determined at specific
times throughout the study. The primary end point was the proportion of successful
patients over the total number of evaluable patients (ie, patients with evaluable
testosterone concentrations at all monthly assessments and no missing values due to
treatment-related adverse events). Treatment success was defined as testosterone suppression below the clinical castration level (ie,
≤0.5 ng/mL) at day 28 and maintenance of clinical castration until study completion
(day 168). The frequency of patients with testosterone concentrations ≤0.2 ng/mL was
also studied.
Results: The study included 160 patients with a mean (SD) age of 71.6 (9.2) years, weight
of 83.7 (15.5) kg, and predominantly white race (87.5% [140/160]). All 160 patients
received at least one dose of study drug; 157 of them were fully evaluable, and 152
completed the study. The proportion of successful patients over the total number of
evaluable patients was 96.8% (152/157; 95% CI,92.7%–99.0%). Five of the 157 evaluable
patients (3.2%) did not achieve the primary end point of testosterone concentration
≤0.5 ng/mL by day 28. Of the evaluable patients, 78.7% (122/155) achieved testosterone
suppression by day 21. By day 28, 96.8% (151/156) of the evaluable patients had achieved
castrate levels, and 73.1% (114/156) achieved testosterone concentrations <0.2 ng/mL.
At study end, 100% (152/152) of the patients completing the study maintained castrate
levels, and 92.8% (141/152) had testosterone concentrations ≤0.2 ng/mL. The pharmacokinetic
profile of leuprolide during the first 3 months of treatment, evaluated in a subset
of the study population (n = 12), showed sustained release of leuprolide from the
formulation. Values for AUC0−t calculated from day 0 to day 28, days 28 to 56, and days 56 to 84 were 25,976.5 (7892.0),
30,685.5 (9348.4), and 31,030.9 (10,745.0) pg/mL per day, respectively. The most common
treatment-related adverse event was hot flashes (45.0% [72/160]). Fatigue, hyperhidrosis,
night sweats, and headache each occurred in ≤6.3% (10/160) of the patients. The most
frequently reported local adverse reaction was pain at the injection site, experienced
by 8.1% (13/160) of the patients.
Conclusions: Leuprolide acetate 3.75-mg depot was effective in achieving and maintaining testosterone
suppression and was well tolerated throughout the study in this cohort of patients
with prostate cancer. ClinicalTrials.gov identifier: NCT00128531.
Key words
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Article info
Publication history
Accepted:
March 8,
2010
Footnotes
Material from this study has been presented at the following meetings: 45th Annual Meeting of the American Society of Clinical Oncology, May 29 June 2, 2009, Orlando, Florida; 30th Congress of the Société Internationale d'Urologie, November 1–5, 2009, Shanghai, China (poster presentation); and the 10th Annual Meeting of the Society of Urologic Oncology in conjunction with the World Urological Oncology Federation, December 3–5, 2009, Bethesda, Maryland (poster presentation).
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© 2010 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
