Literature DB >> 30941562

A phase 3, open-label, multicenter study of a 6-month pre-mixed depot formulation of leuprolide mesylate in advanced prostate cancer patients.

Neal Shore1, Ivan Mincik2, Mark DeGuenther3, Vladimir Student4, Mindaugas Jievaltas5, Jitka Patockova6, Kelle Simpson6, Chu-Hsuan Hu6, Shih-Tsung Huang7, Yuhua Li8, Yisheng Lee8, Ben Chien8, John Mao8.   

Abstract

OBJECTIVES: To determine the safety, efficacy and pharmacokinetic (PK) profile of a pre-mixed depot formulation of leuprolide mesylate subcutaneous injectable suspension (LMIS) 50 mg for up to 1 year of treatment for subjects with advanced prostate cancer. PATIENTS AND METHODS: In this open-label, multicenter study, prostate cancer patients with indication for androgen ablation therapy received two subcutaneous injection of LMIS 50 mg 6 months apart and were followed for an additional 6 months. Two efficacy primary end points were the percentage of subjects with a serum testosterone level ≤ 50 ng/dL by Day 28 as well as the percentage of subjects with similar testosterone suppression from Day 28 to Day 336.
RESULTS: Of the 137 enrolled subjects, 15 (10.9%) subjects did not complete the study, including 5 subjects who terminated early due to an adverse event. By Day 28, 98.5% (95% confidence interval 94.8-99.8) of the subjects achieved a castrate testosterone level. At the end of the study, 97% and 95.9% of the subjects had serum testosterone level ≤ 50 ng/dL and ≤ 20 ng/dL, respectively. LMIS 50 mg significantly reduced serum prostate-specific antigen levels after its first injection and this PSA declination effect remained until the end of the study. No statistically significant change was observed in worsening bone pain or urinary symptom assessments during the study. Hot flush (48.9%) and hypertension (14.6%) were the two most common adverse events reported.
CONCLUSIONS: LMIS 50 mg, administered at 6-month intervals, effectively suppressed serum testosterone level, and demonstrated a consistent safety profile.

Entities:  

Keywords:  Androgen deprivation therapy; Leuprolide acetate; Luteinizing hormone–releasing hormone agonist; PSA; Prostate cancer; Testosterone

Mesh:

Substances:

Year:  2019        PMID: 30941562      PMCID: PMC6954127          DOI: 10.1007/s00345-019-02741-7

Source DB:  PubMed          Journal:  World J Urol        ISSN: 0724-4983            Impact factor:   4.226


  16 in total

1.  Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941.

Authors:  Charles Huggins; Clarence V Hodges
Journal:  J Urol       Date:  2002-07       Impact factor: 7.450

Review 2.  Gonadotropin-releasing hormone and its analogues.

Authors:  P M Conn; W F Crowley
Journal:  N Engl J Med       Date:  1991-01-10       Impact factor: 91.245

3.  Cross-trial comparisons in the oncology arena: when is this justified?

Authors:  Maurie Markman
Journal:  Oncology       Date:  2011-06-14       Impact factor: 2.935

4.  Intermittent androgen suppression for rising PSA level after radiotherapy.

Authors:  Juanita M Crook; Christopher J O'Callaghan; Graeme Duncan; David P Dearnaley; Celestia S Higano; Eric M Horwitz; Eliot Frymire; Shawn Malone; Joseph Chin; Abdenour Nabid; Padraig Warde; Thomas Corbett; Steve Angyalfi; S Larry Goldenberg; Mary K Gospodarowicz; Fred Saad; John P Logue; Emma Hall; Paul F Schellhammer; Keyue Ding; Laurence Klotz
Journal:  N Engl J Med       Date:  2012-09-06       Impact factor: 91.245

5.  Comparison of single-agent androgen suppression for advanced prostate cancer.

Authors:  Herbert Lepor
Journal:  Rev Urol       Date:  2005

6.  EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer.

Authors:  Philip Cornford; Joaquim Bellmunt; Michel Bolla; Erik Briers; Maria De Santis; Tobias Gross; Ann M Henry; Steven Joniau; Thomas B Lam; Malcolm D Mason; Henk G van der Poel; Theo H van der Kwast; Olivier Rouvière; Thomas Wiegel; Nicolas Mottet
Journal:  Eur Urol       Date:  2016-08-31       Impact factor: 20.096

7.  A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer.

Authors:  E David Crawford; Oliver Sartor; Franklin Chu; Ramon Perez; Gary Karlin; J Steve Garrett
Journal:  J Urol       Date:  2006-02       Impact factor: 7.450

8.  Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists.

Authors:  G Tolis; D Ackman; A Stellos; A Mehta; F Labrie; A T Fazekas; A M Comaru-Schally; A V Schally
Journal:  Proc Natl Acad Sci U S A       Date:  1982-03       Impact factor: 11.205

Review 9.  Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth.

Authors:  Abraham Morgentaler; Abdulmaged M Traish
Journal:  Eur Urol       Date:  2008-09-24       Impact factor: 20.096

10.  Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer.

Authors:  A Spitz; J M Young; L Larsen; C Mattia-Goldberg; J Donnelly; K Chwalisz
Journal:  Prostate Cancer Prostatic Dis       Date:  2011-10-25       Impact factor: 5.554

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