Anaplastic ependymoma is associated with a higher incidence of tumor recurrence and its prognosis still remains unsatisfactory. Consolidated therapy for ependymoma includes surgery followed by focal radiotherapy when resection is incomplete. In the case of relapse treatment, options are limited especially for patients who have already received radiotherapy. We sought to establish the feasibility of administering low-dose oral etoposide (50 mg/m(2)/day for 21 days) in combination with the implantation of intracavitary carmustine (BCNU) wafers (Gliadel) at the gross total resection for achieving synergistic treatment in three children affected by recurrent anaplastic ependymoma. All patients had Karnofsky performance scale (KPS) scores >80%. The therapy was tolerated safely and well in all patients without any post-surgery complications. After BCNU wafer implantation, all patients achieved radiological and clinical stabilization for an average period of 3 months. Two patients relapsed after 4 months as shown in brain MRIs. The other patient went to progression two months after the Gliadel implantation. This multimodal approach was not effective for the treatment of refractory anaplastic ependymoma and further studies are required in order to define the role of the combination of multidrug systemic chemotherapy with BCNU wafer implantation in children with high-risk brain tumors.