Hydroxyurea for recurrent surgery and radiation refractory high-grade meningioma

Abstract

Hydroxyurea (HU), an orally administered chemotherapy, has become the de facto standard chemotherapeutic agent in patients with surgically and radiation refractory meningiomas based on a limited literature. A retrospective case series of 35 patients with recurrent WHO Grade 2 (n = 22) or 3 (n = 13) meningioma treated with HU following progression after surgery and radiotherapy was collated with primary study objectives of overall response rate, median and progression free survival (PFS) at 6-months. Thirty-five patients (25 women; 10 men: median age 63 years, range 34-86) with recurrent high-grade meningioma were treated with HU (1,000 mg/m(2) orally divided twice per day; one cycle operationally defined as 4 weeks of daily HU). Patients had progressed radiographically after prior therapy with surgery (35/35) and radiotherapy (35/35: external beam radiotherapy 35/35; stereotactic radiotherapy 35/35). No patient received prior chemotherapy or targeted therapy before instituting HU. Patients received 0.5-7 cycles (median 2.0) of HU with modest toxicity (28.5% all grades and 8.5% grade 3+ anemia or fatigue). There were no radiographic responses, 43% of patients had stable disease and 57% manifested progressive disease at first evaluation. The overall PFS was 3.0% at 6 months (median PFS 2.0 months; 95% CI 1.6-2.4). The majority of patients (80%) following progression on HU were subsequently treated on an investigational trial. In this retrospective series, HU though well tolerated and convenient appeared to have very limited activity, raise questions of what constitutes effective salvage therapy and indicates an unmet need for alternative treatments for recurrent high-grade meningiomas.