Literature DB >> 18448745

CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial.

Eric D Levens1, Clariss Potlog-Nahari, Alicia Y Armstrong, Robert Wesley, Ahalya Premkumar, Diana L Blithe, Wendy Blocker, Lynnette K Nieman.   

Abstract

OBJECTIVE: To evaluate whether 3-month administration of CDB-2914, a selective progesterone receptor modulator, reduces leiomyoma size and symptoms.
METHODS: Premenopausal women with symptomatic uterine leiomyomata were randomly assigned to CDB-2914 at 10 mg (T1) or 20 mg (T2) daily or to placebo (PLC) for 3 cycles or 90-102 days if no menses occurred. The primary outcome was leiomyoma volume change determined by magnetic resonance imaging at study entry and within 2 weeks of hysterectomy. Secondary outcomes included the proportion of amenorrhea, change in hemoglobin and hematocrit, ovulation inhibition, and quality-of-life assessment.
RESULTS: Twenty-two patients were allocated, and 18 completed the trial. Age and body mass index were similar among groups. Leiomyoma volume was significantly reduced with CDB-2914 administration (PLC 6%; CDB-2914 -29%; P=.01), decreasing 36% and 21% in the T1 and T2 groups, respectively. During treatment, hemoglobin was unchanged, and the median estradiol was greater than 50 pg/mL in all groups. CDB-2914 eliminated menstrual bleeding and inhibited ovulation (% ovulatory cycles: CDB-2914, 20%; PLC, 83%; P=.001). CDB-2914 improved the concern scores of the uterine leiomyoma symptom quality-of-life subscale (P=.04). One CDB-2914 woman developed endometrial cystic hyperplasia without evidence of atypia. No serious adverse events were reported.
CONCLUSION: Compared with PLC, CDB-2914 significantly reduced leiomyoma volume after three cycles, or 90-102 days. CDB-2914 treatment resulted in improvements in the concern subscale of the Uterine Fibroid Symptom Quality of Life assessment. In this small study, CDB-2914 was well-tolerated without serious adverse events. Thus, there may be a role for CDB-2914 in the treatment of leiomyomata. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,www.clinicaltrials.gov, NCT00290251 LEVEL OF EVIDENCE: I.

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Year:  2008        PMID: 18448745      PMCID: PMC2742990          DOI: 10.1097/AOG.0b013e3181705d0e

Source DB:  PubMed          Journal:  Obstet Gynecol        ISSN: 0029-7844            Impact factor:   7.661


  18 in total

1.  Effects of GnRH analogues, 'add-back' steroid therapy, antiestrogen and antiprogestins on leiomyoma and myometrial smooth muscle cell growth and transforming growth factor-beta expression.

Authors:  N Chegini; C Ma; X M Tang; R S Williams
Journal:  Mol Hum Reprod       Date:  2002-12       Impact factor: 4.025

2.  Luteal phase dose-response relationships of the antiprogestin CDB-2914 in normally cycling women.

Authors:  Maureen D Passaro; Johann Piquion; Nancy Mullen; Dorette Sutherland; Suoping Zhai; William D Figg; Richard Blye; Lynnette K Nieman
Journal:  Hum Reprod       Date:  2003-09       Impact factor: 6.918

3.  In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone.

Authors:  Barbara J Attardi; Janet Burgenson; Sheri A Hild; Jerry R Reel
Journal:  J Steroid Biochem Mol Biol       Date:  2004-03       Impact factor: 4.292

4.  The frequency of uterine leiomyomas.

Authors:  S F Cramer; A Patel
Journal:  Am J Clin Pathol       Date:  1990-10       Impact factor: 2.493

Review 5.  Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids.

Authors:  A Lethaby; B Vollenhoven; M Sowter
Journal:  Cochrane Database Syst Rev       Date:  2001

6.  Hysterectomy rates in the United States 1990-1997.

Authors:  Cynthia M Farquhar; Claudia A Steiner
Journal:  Obstet Gynecol       Date:  2002-02       Impact factor: 7.661

7.  The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata.

Authors:  James B Spies; Karin Coyne; Noureddine Guaou Guaou; Deneane Boyle; Kerry Skyrnarz-Murphy; Sheila M Gonzalves
Journal:  Obstet Gynecol       Date:  2002-02       Impact factor: 7.661

8.  Production of prolactin by smooth muscle cells cultured from human uterine fibroid tumors.

Authors:  R A Nowak; M S Rein; L J Heffner; A J Friedman; A H Tashjian
Journal:  J Clin Endocrinol Metab       Date:  1993-05       Impact factor: 5.958

Review 9.  Systematic review of mifepristone for the treatment of uterine leiomyomata.

Authors:  Jody Steinauer; Elizabeth A Pritts; Rebecca Jackson; Alison F Jacoby
Journal:  Obstet Gynecol       Date:  2004-06       Impact factor: 7.661

Review 10.  Etiology and pathogenesis of uterine leiomyomas: a review.

Authors:  Gordon P Flake; Janet Andersen; Darlene Dixon
Journal:  Environ Health Perspect       Date:  2003-06       Impact factor: 9.031

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  43 in total

1.  Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations.

Authors:  James H Segars; Estella C Parrott; Joan D Nagel; Xiaoxiao Catherine Guo; Xiaohua Gao; Linda S Birnbaum; Vivian W Pinn; Darlene Dixon
Journal:  Hum Reprod Update       Date:  2014-01-08       Impact factor: 15.610

2.  A-Kinase Anchoring Protein 13 (AKAP13) Augments Progesterone Signaling in Uterine Fibroid Cells.

Authors:  Sinnie Sin Man Ng; Soledad Jorge; Minnie Malik; Joy Britten; Szu-Chi Su; Charles R Armstrong; Joshua T Brennan; Sydney Chang; Kimberlyn Maravet Baig; Paul H Driggers; James H Segars
Journal:  J Clin Endocrinol Metab       Date:  2019-03-01       Impact factor: 5.958

Review 3.  The role of progesterone signaling in the pathogenesis of uterine leiomyoma.

Authors:  J Julie Kim; Elizabeth C Sefton
Journal:  Mol Cell Endocrinol       Date:  2011-06-06       Impact factor: 4.102

Review 4.  Medical treatment of uterine leiomyoma.

Authors:  Mohamed Sabry; Ayman Al-Hendy
Journal:  Reprod Sci       Date:  2012-02-28       Impact factor: 3.060

5.  Periprocedural outcomes comparing fibroid embolization and focused ultrasound: a randomized controlled trial and comprehensive cohort analysis.

Authors:  Emily P Barnard; Ahmed M AbdElmagied; Lisa E Vaughan; Amy L Weaver; Shannon K Laughlin-Tommaso; Gina K Hesley; David A Woodrum; Vanessa L Jacoby; Maureen P Kohi; Thomas M Price; Angel Nieves; Michael J Miller; Bijan J Borah; Krzysztof R Gorny; Phyllis C Leppert; Lisa G Peterson; Elizabeth A Stewart
Journal:  Am J Obstet Gynecol       Date:  2017-01-05       Impact factor: 8.661

Review 6.  The impact of uterine leiomyomas on reproductive outcomes.

Authors:  H Cook; M Ezzati; J H Segars; K McCarthy
Journal:  Minerva Ginecol       Date:  2010-06

Review 7.  The expression and potential regulatory function of microRNAs in the pathogenesis of leiomyoma.

Authors:  Xiaoping Luo; Nasser Chegini
Journal:  Semin Reprod Med       Date:  2008-10-24       Impact factor: 1.303

8.  The selective progesterone receptor modulator CDB4124 inhibits proliferation and induces apoptosis in uterine leiomyoma cells.

Authors:  Xia Luo; Ping Yin; John S Coon V; You-Hong Cheng; Ronald D Wiehle; Serdar E Bulun
Journal:  Fertil Steril       Date:  2010-01-08       Impact factor: 7.329

9.  Emergency contraception: potential role of ulipristal acetate.

Authors:  Kristina Gemzell-Danielsson; Chun-Xia Meng
Journal:  Int J Womens Health       Date:  2010-08-09

Review 10.  Tracking progesterone receptor-mediated actions in breast cancer.

Authors:  Todd P Knutson; Carol A Lange
Journal:  Pharmacol Ther       Date:  2013-11-26       Impact factor: 12.310

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