Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningioma.
OBJECTIVE
The management of certain meningiomas of the skull base and those involving the dural venous sinuses remains a challenge. In recent reports it has been suggested that hydroxyurea chemotherapy can cause regression of unresectable and recurrent meningiomas. The authors report their experience in using hydroxyurea for the treatment of patients with recurrent or unresectable meningiomas.


METHODS
Hydroxyurea was administered at a dosage of approximately 20 mg/kg/day to 11 women and nine men (median age 59 years, range 31-75 years) with recurrent or unresectable intracranial meningiomas (12 basal, two parasagittal, and six multiple). In 16 patients the meningiomas were benign, in three they had atypical features, and in one the meningioma was malignant. All patients had measurable residual disease. Four patients with benign meningiomas had previously received radiotherapy (two were treated with conventional fractionated radiotherapy and two with stereotactic radiosurgery), three with atypical meningiomas received conventional fractionated radiotherapy, and the one with a malignant meningioma received conventional radiotherapy with additional stereotactic radiosurgery. Tumor enlargement was documented in all patients on neuroimages obtained before initiation of hydroxyurea therapy. All patients were evaluable for response to therapy. In 12 patients with benign meningiomas, the disease had stabilized on neuroimages obtained posttreatment (median duration of treatment 122 weeks, range 8-151 weeks), and two of these showed clinical improvement. One patient with a benign meningioma experienced a minor partial response that was noted after 39 weeks of treatment and was confirmed on neuroimaging and clinical evaluations. In three others with benign meningiomas, progression was confirmed on neuroimages obtained after 41, 55, and 66 weeks, respectively: the 1-year freedom from progression rate was 0.93 (standard error 0.07) in patients with benign meningiomas. In three patients with atypical meningiomas, the tumors had progressed on neuroimages obtained after 12, 19, and 45 weeks, respectively. In the patient with a malignant meningioma, progression was confirmed on neuroimages obtained at 24 weeks. Hydroxyurea has been reasonably well tolerated, although one patient discontinued therapy because of moderate myelosuppression.


CONCLUSIONS
Although tumor regression appears uncommon, these results indicate that hydroxyurea may arrest progression of unresectable or recurrent benign meningiomas.
Department of Medicine, Princess Margaret Hospital, and University of Toronto, Ontario, Canada. warren.mason@uhn.on.ca
Warren P
WP
Mason
Fred
F
Gentili
David R
DR
Macdonald
Subramanian
S
Hariharan
Charlene R
CR
Cruz
Lauren E
LE
Abrey
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D017567:Karnofsky Performance Status; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology* / Q000601:surgery; D008579:Meningioma / Q000188:drug therapy* / Q000503:physiopathology* / Q000601:surgery; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000503:physiopathology* / Q000601:surgery; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D006918:Hydroxyurea