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Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies

Authors Spitz A, Gittelman M, Karsh L, Dragnic S, Soliman A, Lele A, Gruca D, Norton M

Received 27 April 2016

Accepted for publication 14 June 2016

Published 23 August 2016 Volume 2016:8 Pages 159—164


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Jan Colli

Aaron Spitz,1 Marc Gittelman,2 Lawrence I Karsh,3 Sanja Dragnic,4 Ahmed M Soliman,5 Aditya Lele,6 Damian Gruca,7 Michael Norton4

1Orange County Urology Associates, Laguna Beach, CA, 221st Century Oncology/UroMedix-Aventura Division, Aventura, FL, 3The Urology Center of Colorado, Denver, CO, 4US Medical Affairs, 5Health Economics and Outcomes Research, 6Data and Statistical Sciences, AbbVie Inc., North Chicago, IL, USA; 7Global Medical Affairs, AbbVie Deutschland, Ludwigshafen, Germany

Introduction: Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels.
Methods: In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks.
Results: Pooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks.
Conclusion: Both 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted.

Keywords: androgen deprivation therapy, gonadotropin-releasing hormone analog, prostate cancer, castrate levels

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