RESUMEN
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.
RESUMEN
Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT) use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as "prostate cancer" and "androgen deprivation therapy", "cardiovascular risk", "lean body mass", "exercise", and "diet". The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to provide effective, accessible, and relatively inexpensive strategies for mitigating ADT-associated toxicities without introducing additional adverse effects.
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For nearly three decades, gonadotropin-releasing hormone (GnRH) agonists, particularly leuprorelin acetate (LA), have served as an important part of the treatment armamentarium for prostate cancer. The introduction of LA depot formulations provided a significant improvement in the acceptance of this therapy; however, their indicated treatment duration of 1 to 4 months was still not long enough to satisfy all medical needs. For this reason some manufacturers developed new injectable formulations that provide testosterone suppression for 6 months. This review article assesses key publications in order to compare these long-acting, commercially available, LA depot formulations and their clinical performance. The literature search identified 14 publications; by excluding reviews, duplications, and non-English articles, only three original papers describing clinical trial remained for review: two focused on microsphere-based LA formulations with either a 30 mg or 45 mg dose and one focused on a gel-based leuprorelin acetate with a 45 mg dose. All products were tested in individual clinical trials and have demonstrated their efficacy and safety.
Asunto(s)
Antineoplásicos Hormonales/química , Antineoplásicos Hormonales/farmacología , Leuprolida/química , Leuprolida/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Química Farmacéutica , Humanos , MasculinoRESUMEN
Androgen deprivation therapy is commonly used in men with advanced prostate cancer; however, it is associated with many short- and long-term side-effects. Intermittent androgen deprivation therapy was first suggested as an alternative regimen in the early 1990s and is now part of treatment guidelines as a result of its ability to reduce adverse events associated with continuous androgen deprivation therapy without decreasing its efficacy. Although many publications evaluated intermittent androgen deprivation therapy's efficacy, the safety and tolerability information of this regimen is relatively limited. The goal of this literature review was to analyze clinical trials that have reported safety and tolerability data in prostate cancer patients treated with intermittent androgen deprivation therapy, as well as assessing quality of life outcomes. A literature search was carried out using biomedical and pharmaceutical databases for published information comparing intermittent androgen deprivation therapy with continuous androgen deprivation therapy. A total of 13 randomized and non-randomized studies were selected and reviewed based on their relevance to the safety, tolerability and quality of life of intermittent androgen deprivation therapy. Benefits for intermittent androgen deprivation therapy were observed for the short-term side-effects (hot flushes and sexual functions) mainly during the off-treatment phase, whereas the data for the long-term side-effects were not as conclusive. Quality of life evaluations are more in support of intermittent androgen deprivation therapy. Although there are some safety, tolerability and quality of life benefits associated with intermittent androgen deprivation therapy, the overall evidence is still limited.