BACKGROUND: Mifepristone (RU486) is an oral antiprogestational and, to a lesser extent, antiglucocorticoid agent commonly used for short-term (single-day) therapy. However, treatment of neoplasms or chronic conditions will require long-term administration. Meningioma is a benign central nervous system tumor that is often progesterone-but not estrogen-receptor positive, making long-term antiprogestational therapy a logical treatment strategy. METHODS: Patients with unresectable meningioma were treated with oral mifepristone 200 mg/day. This dose was selected to provide significant antiprogestational but not antiglucocorticoid activity. Patients also received oral dexamethasone 1 mg/day for the first 14 days. Serial follow-up allowed evaluation for tolerability and side effects of long-term therapy as well as observation for efficacy (tumor shrinkage or improvement in visual fields). RESULTS: Twenty-eight patients received daily oral mifepristone for a total of 1,626 patient-months of treatment. The median duration of therapy was 35 months (range 2-157 months). Repeated oral administration was well tolerated with mild fatigue (22 patients), hot flashes (13 patients), and gynecomastia/breast tenderness (6 patients) being the most common side effects. However, endometrial hyperplasia or polyps were documented in 3 patients and one patient developed peritoneal adenocarcinoma after 9 years of therapy. Minor responses (improved automated visual field examination or improved CT or MRI scan) were noted in 8 patients, 7 of whom were male or premenopausal female. CONCLUSIONS: Long-term administration of mifepristone is feasible and clinically well tolerated, with generally mild toxicity. However, endometrial hyperplasia was noted in several patients. In view of the association between long-term treatment with tamoxifen (another agent that can induce an unopposed estrogen effect) and endometrial cancer, this observation will require further investigation and screening. Minor regression of meningioma that can result in significant clinical benefit is suggested in the male and premenopausal female subgroups of patients.
BACKGROUND:Mifepristone (RU486) is an oral antiprogestational and, to a lesser extent, antiglucocorticoid agent commonly used for short-term (single-day) therapy. However, treatment of neoplasms or chronic conditions will require long-term administration. Meningioma is a benign central nervous system tumor that is often progesterone-but not estrogen-receptor positive, making long-term antiprogestational therapy a logical treatment strategy. METHODS:Patients with unresectable meningioma were treated with oral mifepristone 200 mg/day. This dose was selected to provide significant antiprogestational but not antiglucocorticoid activity. Patients also received oral dexamethasone 1 mg/day for the first 14 days. Serial follow-up allowed evaluation for tolerability and side effects of long-term therapy as well as observation for efficacy (tumor shrinkage or improvement in visual fields). RESULTS: Twenty-eight patients received daily oral mifepristone for a total of 1,626 patient-months of treatment. The median duration of therapy was 35 months (range 2-157 months). Repeated oral administration was well tolerated with mild fatigue (22 patients), hot flashes (13 patients), and gynecomastia/breast tenderness (6 patients) being the most common side effects. However, endometrial hyperplasia or polyps were documented in 3 patients and one patient developed peritoneal adenocarcinoma after 9 years of therapy. Minor responses (improved automated visual field examination or improved CT or MRI scan) were noted in 8 patients, 7 of whom were male or premenopausal female. CONCLUSIONS: Long-term administration of mifepristone is feasible and clinically well tolerated, with generally mild toxicity. However, endometrial hyperplasia was noted in several patients. In view of the association between long-term treatment with tamoxifen (another agent that can induce an unopposed estrogen effect) and endometrial cancer, this observation will require further investigation and screening. Minor regression of meningioma that can result in significant clinical benefit is suggested in the male and premenopausal female subgroups of patients.
Authors: David A Reardon; Andrew D Norden; Annick Desjardins; James J Vredenburgh; James E Herndon; April Coan; John H Sampson; Sridharan Gururangan; Katherine B Peters; Roger E McLendon; Julie A Norfleet; Eric S Lipp; Jan Drappatz; Patrick Y Wen; Henry S Friedman Journal: J Neurooncol Date: 2011-09-22 Impact factor: 4.130
Authors: Nicole M Kretzer; Milu T Cherian; Chengjian Mao; Irene O Aninye; Philip D Reynolds; Rachel Schiff; Paul J Hergenrother; Steven K Nordeen; Elizabeth M Wilson; David J Shapiro Journal: J Biol Chem Date: 2010-11-01 Impact factor: 5.157
Authors: Richard G Everson; Yuuri Hashimoto; Jacob L Freeman; Tiffany R Hodges; Jason Huse; Shouhao Zhou; Joanne Xiu; David Spetzler; Nader Sanai; Lyndon Kim; Santosh Kesari; Andrew Brenner; Franco De Monte; Amy Heimberger; Shaan M Raza Journal: J Neurooncol Date: 2018-05-30 Impact factor: 4.130
Authors: Thomas Kaley; Igor Barani; Marc Chamberlain; Michael McDermott; Katherine Panageas; Jeffrey Raizer; Leland Rogers; David Schiff; Michael Vogelbaum; Damien Weber; Patrick Wen Journal: Neuro Oncol Date: 2014-02-04 Impact factor: 12.300
Authors: Jeffrey J Raizer; Sean A Grimm; Alfred Rademaker; James P Chandler; Kenji Muro; Irene Helenowski; Laurie Rice; Katie McCarthy; Sandra K Johnston; Maciej M Mrugala; Marc Chamberlain Journal: J Neurooncol Date: 2014-01-22 Impact factor: 4.130
Authors: Annette Wilisch-Neumann; Doreen Pachow; Maren Wallesch; Astrid Petermann; Frank D Böhmer; Elmar Kirches; Christian Mawrin Journal: J Cancer Res Clin Oncol Date: 2014-05-11 Impact factor: 4.553