Phase II study of hydroxyurea for unresectable meningioma (Southwest Oncology Group S9811)
2063 Background: Meningiomas account for 15%-18% of CNS tumors. Although benign, recurrence is seen in 16%-39% of cases, depending on the extent of resection possible. Tumor location may make further resection hazardous. Chronic hydroxyurea (HU) was reported to produce well documented objective responses in a small series of patients, with gradual regression occurring over 6–10 months. Induction of apoptosis was furthermore demonstrated with HU in primary benign meningioma explant cultures. The S9811 phase II trial was undertaken to estimate the objective response rate, if any, of unresectable benign meningioma to this HU regimen. Methods: Eligibility required unresectable, measurable, residual or recurrent, histologically-proven benign meningioma. Progressive tumor or progressive neurologic deficit was required. No prior cytotoxics, no radiation therapy for >1 year. Age > 18, adequate hematologic reserve, PS 0–2. HU 20 mg/kg/day po was given for up to 2 years if there was no progressive disease. Single-stage accrual of 38 pts would have allowed detection of 5% null hypothesis response probability vs. 20% with 90% power; the 28 pts actually accrued provide 81% power. Results: Between November 98 and June 2005, 29 pts were accrued, with study closure due to slow accrual. 1 ineligible. Response assessment showed CR+PR 0% (95% CI 0–12%); SD 71% (95% CI 51–87%); PD 21% (95% CI 8–41%); undetermined 7%. Median PFS was 27 months. (95% CI 12–29 months.); 3-year PFS 43% (95% CI 25–61%). Median OS has not been reached. Seven patients were removed from study for toxicity (5/7 hematological). Toxicity was mainly hematologic: 11/28 (39%) grade 3, 2/28 (11%) grade 4. Grade 3 non-hematologic toxicity was seen in 7/28 (25%). Conclusions: Chronic HU therapy for unresectable benign meningioma resulted in an estimated objective response rate of < 12%. Whether the stable disease rate seen differs in any way from what can be expected from the natural history of meningioma cannot be determined from this phase II study design. No significant financial relationships to disclose.