Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breast cancer patients

Boccardo, Francesco; Rubagotti, Alessandra; Amoroso, Domenico; Agostara, Biagio; Amadori, Dino; Gallo, Luigi; Iacobelli, Stéfano; Massidda, B.; Mesiti, M.; Pacini, P; Tomao, Silverio; Paganuzzi, Michela; Marroni, Paola

doi:10.1007/s002800050924

Cited by 18 publications

(10 citation statements)

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“…Free leuprolide is also present in the preparation 6 and is absorbed into the circulation within minutes of injection, while the microspheres slowly release leuprolide, providing steady, suppressive levels. Pharmacokinetic data in adults receiving therapy for prostate 4,5 and breast cancer 7 show that free leuprolide in the depot preparation rapidly enters the serum, peaking at 45 to 60 minutes. In these studies in adult cancer patients, a rise in serum LH and FSH was documented 12 hours after injection but was not studied at earlier time points.…”

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confidence: 99%

Serum Luteinizing Hormone Rises Within Minutes After Depot Leuprolide Injection: Implications for Monitoring Therapy

2002

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ABSTRACT. Objective. To find the time of the serum gonadotropin peak after depot leuprolide injection in children and to show that depot leuprolide therapy can be monitored by measuring serum luteinizing hormone (LH) immediately after injections.Study Design. We measured concentrations of leuprolide, LH, and follicle-stimulating hormone (FSH) at multiple time points before and after the first dose of depot leuprolide in 14 pubertal children beginning therapy. Gonadotropins and sex steroids were measured again after the fourth dose.Results. Serum leuprolide, LH, and FSH levels rose rapidly after initial injection, reaching sustained elevations at 30 to 120 minutes. The median LH level increased from 2.1 mIU/mL at baseline to a peak of 27.5 mIU/mL at 45 minutes, and FSH increased from 5.2 to 16.5 mIU/mL. After 3 months on therapy, median serum LH after depot leuprolide injection was only 0.83 mIU/mL, similar to levels observed after intravenous or subcutaneous gonadotropin-releasing hormone stimulation in comparable subjects on depot leuprolide.Conclusion. Our pharmacokinetic data demonstrate that free leuprolide present in a depot leuprolide injection is equivalent to gonadotropin-releasing hormone in stimulating a rapid rise in serum gonadotropin concentrations. We propose that a single serum sample for LH obtained 30 to 60 minutes after depot leuprolide injection in children provides a convenient and accurate assessment of treatment efficacy. Pediatrics 2002;109(2). URL: http://www.pediatrics.org/cgi/content/full/109/2/e30; puberty, leuprolide, luteinizing hormone, follicle-stimulating hormone, gonadotropin, gonadotropin-releasing hormone.ABBREVIATIONS. CPP, central precocious puberty; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; IM, intramuscular; IV, intravenous; SQ, subcutaneous. C entral precocious puberty (CPP) is the early onset of pubertal development attributable to premature gonadotropin release by the pituitary. Most commonly idiopathic, CPP can also result from central nervous system trauma or tumors. Untreated, precocious puberty can result in short stature and significant social problems for children undergoing sexual maturation years before their peers. 1,2 Pulsatile secretion of endogenous gonadotropin-releasing hormone (GnRH) results in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from the pituitary and progression of puberty, 3 whereas the tonic stimulus of a long-acting GnRH analog causes an initial surge of gonadotropin release, followed by suppression of pituitary gonadotropin production and release. 4,5 Depot leuprolide (Depot-Lupron, TAP Pharmaceuticals, Deerfield, IL), a commonly used long-acting GnRH analog, is given by monthly intramuscular (IM) injection and is slowly released into the circulation to provide such tonic suppressive levels.Depot leuprolide consists of leuprolide encased in microspheres of a glycolic and lactic acid copolymer. Free leuprolide is also present in the preparation 6 and is absorbe...

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Serum Luteinizing Hormone Rises Within Minutes After Depot Leuprolide Injection: Implications for Monitoring Therapy

2002

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“…This is comparable to the original research by Boccardo and colleagues, who were the first to evaluate the endocrinological and clinical activity of a slowrelease formulation of leuprolide acetate in breast cancer patients. 2 A total of 50 pre-or perimenopausal patients with early-or late-stage breast cancer who were candidates for endocrine treatment were included in the study and randomly allocated to receive either when studied in combination with tamoxifen versus chemotherapy plus tamoxifen. 3 This leaves some area of uncertainty in terms of which dose of GnRH agonist is optimal as other trials such as the SOFT/TEXT trials utilized a different GnRH agonist in the form of triptorelin.…”

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confidence: 99%

Efficacy of Different Leuprolide Administration Schedules in Premenopausal Breast Cancer: A Retrospective Review

Kendzierski

Schneider

Kiel

2018

Clinical Breast Cancer

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“…TAP-144-SR (1M) and TAP-144-SR (3M) were effective to suppress the serum E 2 level to a menopausal level in premenopausal breast cancer patients at the same dose at which suppression of serum testosterone to the castrate level was achieved in prostate cancer patients in clinical studies [14–16]. Therefore, the phase III study was conducted at the injection dose of TAP-144-SR (6M) 22.5 mg, which was determined in the phase II study for Japanese treatment-naïve prostate cancer patients [12].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study

et al. 2016

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BackgroundLeuprorelin acetate, a luteinizing hormone-releasing hormone agonist, is used worldwide in premenopausal women with hormone receptor-positive breast cancer. This study was conducted to assess the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer.MethodsThis was a 96-week phase III, randomized, open-label, parallel-group comparative study. All patients concomitantly received oral tamoxifen (20 mg daily). The primary endpoint was the suppression rate of serum estradiol (E2) to the menopausal level (≤30 pg/mL) from Week 4 through Week 48.ResultsIn total, 167 patients were randomized to receive TAP-144-SR (6M) (n = 83) or TAP-144-SR (3M) (n = 84) and the E2 suppression rate was 97.6 and 96.4 %, respectively. The estimated between-group difference was 1.2 % (95 % confidence interval −5.2 to 7.8). The non-inferiority of TAP-144-SR (6M) to TAP-144-SR (3M) for E2 suppression was confirmed. As for safety, common adverse events were hot flush and injection site reactions including induration, pain, and erythema in both treatment groups, which were of ≤Grade 2 in severity and not serious. No significant between-group differences in safety profiles and tolerability were observed.ConclusionsTAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for its suppressive effect on serum E2. TAP-144-SR (6M) was also as well tolerated as TAP-144-SR (3M).

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Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breast cancer patients

Abstract: The present results indicate that the two formulations exert a comparable estrogen-suppressive effect and warrant further study of the 3-monthly formulation of leuprolide acetate in breast cancer patients.

Cited by 18 publications

References 15 publications

Serum Luteinizing Hormone Rises Within Minutes After Depot Leuprolide Injection: Implications for Monitoring Therapy

Serum Luteinizing Hormone Rises Within Minutes After Depot Leuprolide Injection: Implications for Monitoring Therapy

Efficacy of Different Leuprolide Administration Schedules in Premenopausal Breast Cancer: A Retrospective Review

Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study

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