A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors

Tore G. Abrahamsen, Beverly J. Lange, Roger J. Packer, David J. Venzon, Jeffrey C. Allen, Catherine E. Craig, Nicholas J. Patronas, David A. Katz, Joel W. Goldwein, Thomas F. DeLaney, Gregory H. Reaman, Giorgio Perilongo, Peter C. Phillips, Edward H. Oldfield, David G. Poplack, Marc E. Horowitz

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35 Scopus citations


Purpose: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). Methods:Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8–2.25 g/m2/day for 2 days i.v.; total dose 3.6–4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 μg/kg/day s.c.) on days 3–11 or until the absolute granulocyte count reached 1.5 x 109/L. Results: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of <0.5 x 109/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. Conclusions:A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

Original languageEnglish
Pages (from-to)134-139
Number of pages6
JournalJournal of Pediatric Hematology/Oncology
Issue number2
StatePublished - May 1995
Externally publishedYes


  • Astrocytoma
  • Glioblastoma
  • Granulocyte-macrophage colony-stimulating factor
  • High-dose intensity cyclophosphamide
  • Immunosuppression
  • Malignant glioma
  • Medulloblastoma
  • Pediatric oncology
  • Primitive neuroectodermal tumor
  • Thrombocytopenia


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