title: Etoposide, vincristine, and cyclosporin A with standard-dose radiation therapy in newly diagnosed diffuse intrinsic brainstem gliomas: a pediatric oncology group phase I study.
abstract: BACKGROUND
  Brainstem gliomas (BSGs) are resistant to all therapy. Based on their imaging characteristics, we postulated that inhibition of P-glycoprotein (P-gp) associated with endothelial cells of the blood-brain barrier might enhance penetration of xenobiotic antineoplastics.
  
  
  METHODS
  Seven patients were enrolled in a Phase I study of etoposide, continuous infusion cyclosporine A given with and escalating doses of vincristine and concomitant standard-dose irradiation.
  
  
  RESULTS
  Six patients were entered at the first level and one at the second. Closure of the study was mandated by dose-limiting neurotoxicity, consisting of seizures associated with white-matter changes, and alteration of consciousness with bulbar signs. One patient had tumor necrosis at 6 weeks, suggesting some tumor effect. Median survival for the group was 11 months, and for the patients who completed more than 1 month of therapy it was 11 months.
  
  
  CONCLUSIONS
  This regimen proved excessively toxic.
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada. mark.greenberg@sickkids.ca
authors.forename: Mark L
authors.initials: ML
authors.lastname: Greenberg
authors.forename: Paul G
authors.initials: PG
authors.lastname: Fisher
authors.forename: Carolyn
authors.initials: C
authors.lastname: Freeman
authors.forename: David N
authors.initials: DN
authors.lastname: Korones
authors.forename: Mark
authors.initials: M
authors.lastname: Bernstein
authors.forename: Henry
authors.initials: H
authors.lastname: Friedman
authors.forename: Susan
authors.initials: S
authors.lastname: Blaney
authors.forename: Linda
authors.initials: L
authors.lastname: Hershon
authors.forename: Tianni
authors.initials: T
authors.lastname: Zhou
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kretschmar
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D011879:Radiotherapy Dosage; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014750:Vincristine; D005047:Etoposide; D016572:Cyclosporine