The Role of Mifepristone in Meningiomas Management: A Systematic Review of the Literature

Table 2

Study	Year	pts	Purpose	Population	Histology/PR expression	Intervention	Outcome and results	Side effects	Limitations	Conclusion
Grunberg et al. [29]	1991	14	Efficacy of long-term oral therapy with mifepristone in unresectable meningiomas; 11 pts were progressing (radiologically or symptomatically) before starting the TT with mifepristone	Inoperable meningiomas; 6 M; 8 F: (i) 2 premenop; (ii) 6 postmenop	5 meningothelial 3 cellular; 2 fibrous meningioma; 2 malignant meningioma; 2 w/o biopsy; No evaluation of PR expression	Mifepristone 200 mg/d for 2–31 mo; (9 pts more than 12 mo); Dexa 1 mg daily during the first 14 d of treatment	13 pts assessed for response; (1 refused); (i) 5/13 pts radiological regression after at least 6 mo; (ii) 3/13 subjective clinical improvement after 2-3 mo; (iii) 3/13 progression (of which 2 were malignant meningiomas)	14 evaluated; (i) 11/14 fatigue; (ii) 5/14 hot flashes; (iii) 3/6 M gynecomastia; (iv) 2 alopecia; (v) 2 amenorrhea (premenop F); (vi) 1 hypothyroidism	Subjective clinical evaluation; Radiological response evaluated with CT or MRI; Heterogenous population: (i) 2 premenop F; (ii) 6 postmenop F; (iii) 6 men; No evaluation of PR expression; 1 previous RT; 4 previous hormonal therapy (MPA and tamoxifen); For the 3 pts defined as stable before starting mifepristone, the previous FU is ns	PRO
Grunberg et al. [30]	2006	28 (Included the 14 pts of the study of Grunberg et al. 1991 [29])	Clinical tolerance of long-term treatment with mifepristone	9 M; 19 F: (i) 5 premenop; (ii) 14 postmenop	13 meningothelial; 4 fibroblastic; 5 cellular/ns; 2 malignant; 4 not biopsied; No evaluation of PR expression	Mifepristone 200 mg/d for 2–31 mo; Mean FU 35 mo (2–157 mo); Total of 1626 patient-months; Dexa 1 mg daily during the first 14 d of treatment	8/28 pts radiological (5) and clinical (3) improvement; (7/8 were male or premenopausal F)	22/28 pts mild fatigue; 13/28 pts hot flashes; 6/28 pts gynecomastia; 3/28 depression; 1 N/V; 3/28 pts endometrial hyperplasia; 1 pt peritoneal adenocarcinoma	2 malignant meningiomas; 4 no histological diagnosis; No evaluation of PR expression	CON
Lamberts et al. [31]	1992	10	Effect of mifepristone treatment in recurrent or inoperable meningiomas; recent evidence of growing: neuroradiological in 9 cases; ophthalmological in 4 cases	12 recurrent or inoperable meningiomas in 10 pts; 7 pts previous operation; 3 males; 1 premenop F (with NF2); 6 postmenop F	No data about histology nor PR expression	Mifepristone 200 mg/d for 12 mo; 4 cases started Dexa 7.5 mg daily and continued throughout the study	5/12 meningiomas grew (2 deaths); 3/12 stable; 4/12 transient regression (progression at discontinuation of TT); 5/10 pts symptomatic improvement; objective assessment in 2 pts; 1 pt continued to deteriorate	Asthenia, N/V	CT scan evaluation (planimetry); Group of aggressive meningiomas (recent evidence of growing); No data about histology nor PR expression; Graphic over responsive patients; Analyzable in different ways	PRO
De Keizer and Smit [32]	2004	2	Efficacy of long-term mifepristone treatment	Unresectable sphenoid-ridge meningioma; 2 F: 1 postmenop F	Both tumors were PR +	Mifepristone 200 mg/d then increased to 400 mg/d; Dexa 0.5 mg three times daily; FU 14 y	2 controlled tumor growth; 1 improved VA; 1 improved headache, stable VA; clinical deterioration, and radiological growth after TT discontinuation; Initial benefits persist	1 endometrial hyperplasia	CT and MRI evaluation	PRO
Touat et al. [33]	2014	3	Efficacy of mifepristone in meningiomatosis	F, postmenop	Histological examination in one case	Mifepristone 200 mg/d.; FU 4–10 y	3/3 long lasting clinical and 2/3 radiological response or stabilization	1 benign ovarian serous cystadenoma	Small pts; Histological examination just in one case	PRO
Spitz et al. [34]	2005	25	To determine clinical side effects and biochemical abnormalities with long-term mifepristone therapy	16 F and 9 M; 22–80 y; unresectable meningioma		Mifepristone 200 mg/d (follow-up variable from 13 y to 4 mo); Total of 1620 mo	Safety of long-term TT	(i) 22/25 pts fatigue; (ii) 2 endometrial hyperplasia; (iii) 2 endometrial thickening	Varied follow-up; Heterogeneous cohort: 5 premenopausal F, 11 postmenopausal F, and 9 M	PRO
Grunberg et al. [35]	2001	160 (80 per arm)	Efficacy of mifepristone in unresectable meningiomas	Adults with unresectable histologically confirmed nonmalignant meningiomas appeared (22%) or progressing (78%) within 2 y; Median age 57 y; 30% M; 19% premenop F; 51% postmenop F; 29% prior RTH	ns	Blinded administration of mifepristone 200 mg/d versus placebo; Follow-up 2 y	FFP (freedom from progression); Progression defined as anatomic growth or neurologic deterioration; No significant difference in response between the arms: median FFP was 10 mo for mifepristone pts and 12 mo for placebo pts ()	Fatigue (72% mifepristone pts vs 54% placebo pts); Headache; Hot flashes; 9 mifepristone pts had endometrial hyperplasia (16% F)	Limited data available (abstract); No information about histological type and PR expression	CON

CON: against; d: days; dexa: dexamethasone; EGF: epithelial growth factor; ER: estrogen receptors; F: female; M: male; mo: months; : number; ns: not specified; N/V: nausea and vomiting; PR: progesterone receptors; Postmenop: postmenopausal; Premenop: premenopausal; PRO: for, in favor of; Pts: patients; TT: treatment; VA: visual acuity; y: years; w: weeks; w/o: without.