High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children

A Phase Ii chemotherapy trial was conducted in 18 children with recurrent brain tumors, using high doses (80 mg/kg or greater) of intravenous cyclophosphamide cyclophosphamide. All eight patients with medulloblastomas responded; two patients with systemic metastases had complete responses and six others had partial responses. In seven patients with gliomas, there were one complete and four partial responses. In a third group, all three patients with intracranial germ-cell tumors had partial responses. The overall response rate was, therefore, 89% (16 of 18 patients), and the mean duration of response was 7 months (range 2 to 24 or more months). The hematological toxicity was considerable, with two deaths possibly related to chemotherapy: one patient, a recipient of unirradiated packed cells, died from a graft versus host reaction, and the other died from an intracranial hemorrhage during a thrombocytopenic episode. Four patients had prior chemotherapy, and 10 patients had prior neuraxis radiation therapy. These patients tolerated aggressive chemotherapy reasonably well. The results are sufficiently encouraging to justify a Phase III trial in patients with newly diagnosed disease.