Role of hydroxyurea as an adjuvant treatment after Gamma knife radiosurgery for atypical (WHO grade II) meningiomas

Meningioma is an extra axial tumor which is a common primary tumor affecting the CNS (20-30%). Its incidence is between 4 and 6 per 100.00 per year [1,2] . World Health Organization (WHO) categorizes meningiomas into three grades; Grade 1 so called benign meningioma, Grade 2 atypical meningioma and Grade 3 anaplastic meningioma [3] . Anaplastic meningiomas carry a particularly poor prognosis, with a median survival of 1.5 years and a 5-year mortality of 68% [5,6] . An atypical meningioma is a meningioma of intermediate grade between benign and malignant forms [7] . Surgical treatment is the primary therapy, but may be incomplete due to the tumor's location and intimate relation to surrounding structures. [2,4] . The recurrence rate even in totally resected benign tumors is between 10 and 20% after 5 years, 20-30% after 10 years, and about 50% after 20 years. In some patients, surgery may be impossible or associated with an unacceptable morbidity [4] . Long term data using definitive external-beam radiation have demonstrated prolonged tumor control comparable with that observed with surgery followed by adjuvant radiation [7] . However, radiotherapy rarely reduces tumor size and may be complicated by long term side effects [2] . Stereotactic radiotherapy (SRS) has become an alternative option to external-beam radiation for recurrent or partially resected meningiomas and for patients in whom surgery is not an option because of the tumor's location or patient comorbidities [7] . Many chemotherapeutic agents have been investigated, including adriamycin, temozolomide, dacarbazine, ifosfamide, and irinotecan. None have showed conclusive results [12,13] . Hydroxyurea is an oral antimetabolite whose main use is in the treatment of chronic myeloid leukemia. The mechanism of action appears to be inhibition of ribonucleotide reductase causing apoptosis in phase S of the cell cycle [2,6] . The drug is modestly active against meningiomas, well tolerated and induces stable disease. However, there have been no documented objective radiologic responses [4,6]