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

• Published in: Research and reports in urology Vol. 8; pp. 159 - 164
• Main Authors: Spitz, Aaron, Gittelman, Marc, Karsh, Lawrence I, Dragnic, Sanja, Soliman, Ahmed M, Lele, Aditya, Gruca, Damian, Norton, Michael
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Ltd 01.01.2016; Dove Medical Press
• Subjects: androgen deprivation therapy; Androgens; Antigens; Cancer therapies; castrate levels; Chromatography; Clinical trials; FDA approval; gonadotropin-releasing hormone analog; Mass spectrometry; Metastasis; Oncology; Original Research; Prostate cancer; Scientific imaging; Studies; Testosterone; Urology; United States > US; North Chicago Illinois; androgen deprivation therapy; gonadotropin-releasing hormone analog; prostate cancer; castrate levels
• ISSN: 2253-2447; 2253-2447
• DOI: 10.2147/RRU.S111475

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. 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. 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. 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.