Extended release, 6-month formulations of leuprolide acetate for the treatment of advanced prostate cancer: achieving testosterone levels below 20 ng/dl

Abstract

Introduction: Luteinizing hormone-releasing hormone agonists such as leuprolide acetate (LA) are the most frequently utilized treatment of advanced prostate cancer as the regimen for achieving androgen deprivation therapy (ADT). The efficacy of LA is determined by extent of testosterone (T) suppression in prostate cancer patients. Although, the historical castrate T suppression target has been defined as < 50 ng/dl, this level may not be as low as required to deliver equivalent suppression as achieved by surgical castration. Recent studies have demonstrated that a T level as low as 20 ng/dl may produce improved clinical outcomes.

Areas covered: LA is available in long-acting formulations that deliver active drug over the course of 1–6 months from a single-dose administration. The technologies utilized to provide sustained drug delivery differ: one mode of administration uses microspheres, which encapsulate the drug and are injected as a suspension intramuscularly; another mode of administration uses a liquid polymer that creates a single, solid depot after injection subcutaneously. This article will review the safety and efficacy of both 6-month LA formulations, as well as their impact in prostate cancer treatment.

Expert opinion: As the understanding of optimal T castrate level evolves and may be refined pending new data from contemporaneous trials, achievement and maintenance of T levels well below 50 ng/dl may be important in evaluating potential differences in ADT regimens.

Keywords:

• biodegradable polymer
• depot
• leuprolide acetate
• leuprorelin
• microspheres
• prostate cancer

Declaration of interest

ED Crawford is a consultant or advisor for Bayer, MDx, Genomic Health, Janssen, Dendreon, Ferring, and TOLMAR. JW Moul has received honoraria from Dendreon, Ferring, Janssen and TOLMAR, is a consultant or advisor for Myriad, Genomic Health, Theralogix, and is part of the speaker’s bureau for Myriad, Genomic Health, Dendreon, Ferring, Janssen, Sanofi, and TOLMAR. ND Shore is a consultant or advisor for Astellas, Bayer, Dendreon, Ferring, Janssen, Medivation, TOLMAR, Sanofi, and Millennium. O Sartor has been a consultant for TOLMAR, AbbVie, and Atrix, and has been an investigator for Atrix. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing support by Drs. Jocelyn Hybiske and Mark Rocco of Xelay Acumen, Inc. was utilized in the production of this manuscript and funded by TOLMAR Inc, Fort Collins, CO.