DOSE-ESCALATION TRIAL OF CYCLOPHOSPHAMIDE WITH SARGRAMOSTIM IN THE TREATMENT OF CENTRAL-NERVOUS-SYSTEM (CNS) NEOPLASMS

We conducted a dose escalation trial of cyclophosphamide plus Sargramo stim in the therapy of patients with newly diagnosed or recurrent cent ral nervous system tumors. Cyclophosphamide was administered at doses ranging between 1.0 and 2.5 g/m(2) daily for two doses. Sargramostim w as administered at a fixed dose of 250 mu g/m(2) subcutaneously twice a day beginning 24 hours after the second cyclophosphamide dose and co ntinuing through the leukocyte nadir until the absolute neutrophil cou nt (ANC) was > 1,000 cell/mu l for two consecutive days. The MTD for p atients who had not received any prior chemotherapy and who had receiv ed either no radiotherapy or radiotherapy confined to the cranium was 2.0 g/m(2) daily for two doses. The MTD for patients previously treate d with chemotherapy or neuraxis radiotherapy was also 2.0 g/m(2) daily for two doses. Responses were seen in patients with medulloblastoma ( 8/9), glioblastoma multiforme (2/13), germinoma (1/1), and pineoblasto ma (1/2). (C) 1995 Wiley-Liss, Inc.