Hormone Therapy/Prostate Information
The following information was derived from trials using various GnRH agonists and is not specific to Trelstar®. To confirm the findings below, a prospective, randomized and carefully designed trial to assess clinical progression and mortality as the primary endpoints would be required to reassess the testosterone cutoff level.
The FDA defines medical castration as a serum testosterone level below 50 ng/dL. However, a clinical study using a more modern serum testosterone assay has shown that the testosterone level associated with medical castration may be closer to 20 ng/dL.6 It is important to note that the clinical benefits of maintaining testosterone levels below 20 ng/dL versus 50 ng/dL have not been prospectively studied.
To determine whether testosterone escape during androgen deprivation therapy is clinically relevant, Morote and colleagues conducted a study to identify the serum testosterone level in these patients that, when exceeded, was associated with clinical consequences.7
- Enrolled 73 men with non-metastatic prostate cancer7
- Patients were treated with 3 months of depot luteinizing hormone releasing hormone (LHRH) agonists7
- Serum testosterone and PSA measured every 6 months7
- Serum testosterone ≥20 ng/dL was considered a breakthrough response7
- Androgen-independent progression (AIP) was defined as 3 consecutive rising PSA levels7
Breakthrough increases in serum testosterone occurred frequently
- More than half of the patients had at least one breakthrough testosterone measurement above 20 ng/dL7
Androgen-independent progression was directly related to breakthrough increases in serum testosterone
- Patients whose testosterone remained below castration levels had a longer time to androgen-independent progression than patients who had any breakthrough testosterone increases (P=0.0207)7
- “Breakthrough increases of serum testosterone . . . are not only frequent but also have clinical implications regarding PSA progression.”7
- “This is the first report to establish a direct relationship between testosterone increases and AIP.”7
- “To confirm these findings, a prospective, randomized and carefully designed trial to assess clinical progression and mortality as the primary endpoints would be required to reassess the testosterone cutoff level.”7
- Trelstar® full Prescribing Information, Watson Pharma, Inc.
- Data on file, Watson Pharma, Inc. DEB-TRI6M-301 Clinical Study Report, May 2008.
- Lundström EA, Rencken RK, van Wyk JH, et al. Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study. Clin Drug Investig. 2009;29:757-765.
- Data on file. Watson Pharma, Inc. DEB-96-TRI-01 (first phase) Clinical Study Report; July 1999.
- Data on file. Watson Pharma, Inc. DEB-96-TRI-01 (second phase) Clinical Study Report; June 1999.
- Oefelein MG, Feng A, Scolieri MJ, Ricchiutti D, Resnick MI. Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Urology. 2000;56:1021-1024.
- Morote J, Orsola A, Planas J, et al. Redefining clinically significant castration levels in patients with prostate cancer receiving continuous androgen deprivation therapy. J Urol. 2007;178:1290-1295.
- Heyns CF, Simonin M-P, Grosgurin P, Schall R, Porchet HC. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU International. 2003;92:226-231.
Trelstar® is indicated for the palliative treatment of advanced prostate cancer.
Important Safety Information
The most commonly reported adverse events associated with the use of Trelstar® 22.5 mg included hot flushes (71.7%), erectile dysfunction (10.0%), and testicular atrophy (7.5%) • The most commonly reported adverse events associated with the use of Trelstar® 3.75 mg/Trelstar® 11.25 mg included hot flushes (58.6%/73.0%), skeletal pain (12.1%/13.2%), impotence (7.1%/2.3%), headache (5.0%/6.9%), leg pain (2.1%/5.2%), and edema in legs (0.0%/6.3%) • Trelstar® is contraindicated in women who are or may become pregnant as well as patients who are hypersensitive to triptorelin, other GnRH agonists, or GnRH • Anaphylactic shock, hypersensitivity, and angioedema related to triptorelin administration have been reported • Trelstar® causes an initial transient increase in testosterone levels. Patients may experience the onset or exacerbation of symptoms during this period, including bone pain, neuropathy, hematuria, urethral or bladder outlet obstruction, or spinal cord compression that may contribute to weakness or paralysis with or without fatal complications. Patients with metastatic vertebral lesions and/or urinary tract obstruction should be closely observed. Hyperglycemia and an increased risk of developing diabetes, as well as increased risk of myocardial infarction, sudden cardiac death, and stroke have been reported in men receiving GnRH analogs. Patients should be monitored for blood glucose level and cardiovascular disease, and managed according to current clinical practice
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