Literature DB >> 19241422

Phase 2 trial of mifepristone (RU-486) in advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma.

Lois M Ramondetta1, Alaina J Johnson, Charlotte C Sun, Neely Atkinson, Judith A Smith, Maria S Jung, Russel Broaddus, Revathy B Iyer, Thomas Burke.   

Abstract

BACKGROUND: : The objective of this study was to determine the efficacy of mifepristone (RU-486) in women with advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma (LGESS).
METHODS: : Mifepristone (RU-486; 200 mg orally) was given daily to patients with progesterone receptor-positive advanced or recurrent endometrioid adenocarcinoma or LGESS. Patients were evaluated every 4 weeks for toxicity and response. Quality-of-life data were obtained using the Memorial Symptom Assessment Scale and Functional Assessment for Cancer Therapy.
RESULTS: : Twelve of 13 enrolled patients were evaluable in the first phase of accrual. Stable disease was noted in 3 of 12 patients (at 8 weeks, 12 weeks, and > or =77 weeks, respectively), and the median time to disease progression was 48 days. Among the patients who had stable disease, 2 women had endometrioid endometrial cancer, and 1 woman had LGESS. No partial or complete responses were observed. The most frequent grade 1 and 2 toxicities were anorexia, fatigue, and mood alterations observed in 50%, 50%, and 58% of patients, respectively. The most common grade 3 toxicities were fatigue and dyspnea observed in 25% and 17% of patients, respectively. One patient experienced grade 4 dyspnea. Thirty-three percent of patients had asymptomatic elevations of corticotropin. No serious treatment-related adverse events occurred. There were no significant changes in quality of life.
CONCLUSIONS: : Single-agent mifepristone used in the treatment of recurrent endometrioid adenocarcinoma or LGESS resulted in a stable disease rate of 25%. One patient who had a biopsy-positive disease recurrence remained stable at 77 weeks. Although mifepristone was tolerated well, as a single agent, it provided limited response as a single agent in women with progesterone receptor-positive uterine tumors. Recently, was been recognized that biologic agents used as single agents may result only in stable disease unless they are combined with cytotoxic agents. The authors concluded that further research into the best mode of application for mifepristone in the treatment of endometrial cancer is needed. Cancer 2009. (c) 2009 American Cancer Society.

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Year:  2009        PMID: 19241422     DOI: 10.1002/cncr.24197

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


  11 in total

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Journal:  J Biol Chem       Date:  2010-11-01       Impact factor: 5.157

Review 2.  Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus.

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Review 3.  Treatment of recurrent endometrial stromal sarcoma with letrozole: a case report and literature review.

Authors:  Vonetta T Sylvestre; Charles J Dunton
Journal:  Horm Cancer       Date:  2010-01-29       Impact factor: 3.869

Review 4.  Hormone response in ovarian cancer: time to reconsider as a clinical target?

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Review 5.  Selective Progesterone Receptor Modulators-Mechanisms and Therapeutic Utility.

Authors:  Md Soriful Islam; Sadia Afrin; Sara Isabel Jones; James Segars
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6.  Systems pharmacology of mifepristone (RU486) reveals its 47 hub targets and network: comprehensive analysis and pharmacological focus on FAK-Src-Paxillin complex.

Authors:  Suhong Yu; Xingtian Yang; Yewei Zhu; Fangwei Xie; Yusheng Lu; Ting Yu; Cuicui Yan; Jingwei Shao; Yu Gao; Fan Mo; Guoneng Cai; Patrick J Sinko; Lee Jia
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7.  Molecular mechanisms underlying mifepristone's agonistic action on ovarian cancer progression.

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Journal:  EBioMedicine       Date:  2019-08-26       Impact factor: 8.143

Review 8.  A Hypothetical Model Suggesting Some Possible Ways That the Progesterone Receptor May Be Involved in Cancer Proliferation.

Authors:  Jerome H Check; Diane L Check
Journal:  Int J Mol Sci       Date:  2021-11-16       Impact factor: 5.923

Review 9.  Potential Therapeutic Targets in Uterine Sarcomas.

Authors:  Tine Cuppens; Sandra Tuyaerts; Frédéric Amant
Journal:  Sarcoma       Date:  2015-10-21

Review 10.  Endometrial stromal sarcoma in combination with mixed type endometrial carcinomas: A case report and literature review.

Authors:  Xiao-Xin Xiu; Hua-Li Wang; Lv Yun-Yi; Kong Fan-Dou; Hou Jin-Ping
Journal:  Medicine (Baltimore)       Date:  2017-12       Impact factor: 1.817

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