title: A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors.
abstract: OBJECTIVE
  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 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/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 10(9)/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.
authors.affiliation: Pediatric Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Abrahamsen
authors.forename: B J
authors.initials: BJ
authors.lastname: Lange
authors.forename: R J
authors.initials: RJ
authors.lastname: Packer
authors.forename: D J
authors.initials: DJ
authors.lastname: Venzon
authors.forename: J C
authors.initials: JC
authors.lastname: Allen
authors.forename: C E
authors.initials: CE
authors.lastname: Craig
authors.forename: N J
authors.initials: NJ
authors.lastname: Patronas
authors.forename: D A
authors.initials: DA
authors.lastname: Katz
authors.forename: J W
authors.initials: JW
authors.lastname: Goldwein
authors.forename: T F
authors.initials: TF
authors.lastname: DeLaney
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008297:Male; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy*
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide