title: Long-term administration of mifepristone (RU486): clinical tolerance during extended treatment of meningioma.
abstract: 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.affiliation: Division of Hematology/Oncology, University of Vermont College of Medicine, Burlington, Vermont, USA. steven.grunberg@uvm.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Grunberg
authors.forename: Martin H
authors.initials: MH
authors.lastname: Weiss
authors.forename: Christy A
authors.initials: CA
authors.lastname: Russell
authors.forename: Irving M
authors.initials: IM
authors.lastname: Spitz
authors.forename: Jamshid
authors.initials: J
authors.lastname: Ahmadi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Sadun
authors.forename: Regine
authors.initials: R
authors.lastname: Sitruk-Ware
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy*; D008579:Meningioma / Q000188:drug therapy*; D008875:Middle Aged; D015735:Mifepristone / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D003280:Contraceptives, Oral, Synthetic; D015735:Mifepristone