Efficacy Over Time of LHRH Analogs in the Treatment of PCa—A Prospective Analysis Using Serum Testosterone to Determine Dosing Intervals

Greil, Sabine; Robinson, Eileen A.; Singal, Bonita; Kleer, Eduardo

doi:10.1016/j.urology.2008.08.516

Cited by 7 publications

(6 citation statements)

References 9 publications

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“…Moreover, two clinical trials have shown that depot products often suppress testosterone for longer than the labeled interval 66,67. Accordingly, researchers have begun investigating the clinical merits of intermittent androgen deprivation therapy (IADT) with GnRH agonists.…”

Section: Resultsmentioning

confidence: 99%

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort

Crawford

Phillips²

2011

CMR

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Two different 6-month GnRH agonist depot formulations approved for palliative treatment of advanced and metastatic prostate cancer in the United States – leuprolide acetate 45 mg and triptorelin pamoate 22.5 mg – provide patients with efficacy and safety comparable to those of existing 1-, 3-, and 4-month GnRH agonist depots. However, the 6-month formulations can increase patient convenience, comfort, and compliance by reducing the number of physician visits and injections required. At the conclusion of their pivotal trials, the 6-month formulations demonstrated efficacy rates in achieving chemical castration (serum testosterone ≤50 ng/dL) that ranged between 93% and 99%. As with existing GnRH agonist depot formulations, hot flashes represented the most common adverse event reported in trials of 6-month leuprolide acetate or triptorelin. As such, these products may prove useful not only for their labeled indication, but also as adjuncts to other treatments such as radical prostatectomy, radiotherapy, and chemotherapy. We recommend further research, including head-to-head trials between the 6-month GnRH depots, to refine our understanding of these products.

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Section: Resultsmentioning

confidence: 99%

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort

Crawford

Phillips²

2011

CMR

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“…Indeed, evaluation of testosterone levels several times after initiation of LHRH agonist therapy (at least after 1 and 6 months) can serve several purposes [2, 11]: it can be used (i) to identify patients who fail to achieve testosterone castration levels [12, 13], (ii) to determine the optimal time for LHRH agonist redosing, and (iii) to monitor the potential development of castration-resistant PCa, as several studies have shown that lower serum testosterone levels achieved during ADT are associated with slower progression to castration resistance [14, 15] and a lower risk of dying from PCa [16]. Patients with a parallel increase in PSA and testosterone levels during ADT might benefit from an additional injection of the same or another LHRH analogue (or from surgical orchiectomy), while patients with rising PSA levels despite testosterone levels below the castration level have probably become castration resistant and require a different approach [2, 11]. Both in the current observational study and in the German non-interventional study [9], it was noted that, in routine clinical practice, there is a lack of compliance with these EAU guidelines regarding testosterone monitoring.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard ® /Depo-Eligard ® ) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study

Braeckman¹,

Michielsen²

2014

aoms

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IntroductionThe 1-, 3- and 6- month biodegradable polymer matrix depot formulations of leuprorelin acetate (Eligard®/Depo-Eligard®, Astellas Pharma Inc/BV) were shown to reduce testosterone and prostate-specific antigen levels and to be well tolerated in patients with advanced prostate cancer in several clinical trials. This study aimed at evaluating the efficacy, safety and tolerability of the 1- and 3-month leuprorelin acetate depot formulations in daily clinical practice.Material and methodsA prospective, open-label, non-interventional, phase IV study (MANTA) was conducted in 243 Belgian prostate cancer patients who had been prescribed the 1-month (7.5 mg) or 3-month (22.5 mg) leuprorelin acetate depot formulation. Patients were followed for at least 3 months.ResultsMedian serum prostate-specific antigen levels were reduced by 95% from 12.0 ng/ml at baseline to 0.60 ng/ml after a median follow-up time of 132 days, while median testosterone levels were reduced by 94% from 360 ng/dl to 20 ng/dl. Partial or complete treatment response was observed in 83% of patients at the final visit (according to the physician's assessment). Ninety-two patients (37.86%) experienced treatment-emergent adverse events, with injection site-related reactions, hot flushes and tumor flare being the most common ones. Overall safety and tolerability of the leuprorelin acetate depot formulation were rated as good or excellent by 90% of physicians.ConclusionsThese data are consistent with efficacy and tolerability results from clinical trials. They confirm that the 1- and 3-month leuprorelin acetate depot formulations are well tolerated and reliably lower serum prostate-specific antigen and testosterone levels in routine clinical practice.

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“…Greil et al . [33] added additional evidence to the value of testosterone measurement by determining the dosing intervals for three treatment cycles. They found that testosterone suppression persists for more than 120 days in the first and second cycles and even longer in the subsequent cycles.…”

Section: Intermittent Androgen Deprivationmentioning

confidence: 99%

Testosterone in prostate cancer: the Bethesda consensus

et al. 2011

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What's known on the subject? and What does the study add? Androgen stimulation of prostate cancer (PCa) cells has been the basis for extensive studies evaluating the role of androgen in PCa but the diagnostic measurement of androgen as well as androgen values that potentially influence prognosis are unclear in patients with PCa. The 50 ng/dL threshold has been questioned as a result of reports indicating worse outcomes for levels between 20 and 50 ng/dL. Instead, a 20 ng/dL threshold for serum testosterone after androgren deprivation therapy in patients with advanced PCa was recommended. OBJECTIVE Androgen stimulation of prostate cancer (PCa) cells has been extensively studied. The increasing trend of using serum testosterone as an absolute surrogate for castration state means that the diagnostic measurement of testosterone and the values potentially influencing prognosis must be better understood. This is especially important when PCa progresses from an endocrine to an intracrine status. PATIENTS AND METHODS We performed a literature review using the MEDLINE database for publications on: (i) hormonal changes with androgen deprivation therapy (ADT); (ii) monitoring hormonal therapy with testosterone measurement; (iii) the efficacy of intermittent androgen deprivation (IAD) compared with continuous androgen deprivation; (iv) the underlying mechanisms of castration‐resistance; and (v) novel treatments for castration‐resistant PCa (CRPCa). RESULTS The optimum serum castration levels to be achieved with ADT are still debated. Recently, the 50 ng/dL threshold has been questioned because of reports indicating worse outcomes when levels between 20 and 50 ng/dL were studied. Instead, a 20 ng/dL threshold for serum testosterone after ADT in patients with advanced prostate cancer was recommended. CONCLUSION Understanding the mechanisms of androgen biosynthesis relating to PCa as well as prognostic implications might achieve a consensus regarding the role of ADT for both the androgen‐sensitive and ‐insensitive disease state.

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Efficacy Over Time of LHRH Analogs in the Treatment of PCa—A Prospective Analysis Using Serum Testosterone to Determine Dosing Intervals

Cited by 7 publications

References 9 publications

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort

Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard ® /Depo-Eligard ® ) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study

Testosterone in prostate cancer: the Bethesda consensus

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