title: Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme.
abstract: BACKGROUND
  Glioblastoma multiforme in childhood is rare, and the prognosis for patients with the disease is poor. The Pediatric Oncology Society of the Germanic language group (GPOH) enrolls patients in a series of pilot trials, the first of which is reported here (HIT-GBM-A).
  
  
  METHODS
  Twenty-two patients with glioblastoma multiforme, World Health Organization Grade 4, between the ages of 3-15 years (45% male) were enrolled during the period 1995-1997. There were 13 supratentorial tumors, 8 brainstem tumors, and 1 cerebellar tumor. The patients underwent the following procedures: stereotactic biopsy (n = 3 patients), open biopsy (n = 1 patient), partial resection (n = 6 patients), subtotal resection (n = 4 patients), and macroscopic total resection (n = 8 patients). Adjuvant treatment consisted of oral chemotherapy with trofosfamide, 100 mg/m(2), and etoposide, 25 mg/m(2), daily or for 21-day cycles interrupted by 1-week rests. Standard fractionated radiation (54 grays) was started concurrently with the first cycle.
  
  
  RESULTS
  The chemotherapy was well tolerated, with no treatment-related deaths and only minor side effects. The responses in 12 evaluable patients after two cycles were as follows: 1 complete response, 1 partial response, 3 patients with stable disease, and 7 patients with progressive disease. The median overall survival was 12 months. The 1-year, 2-year, and 4-year overall survival rates were 52%, 26%, and 22%, respectively, and the event free survival rates were 26%, 22%, and 4%, respectively. None of the four surviving patients (3.2 years, 3.4 years, 4.0 years, and 4.2 years after diagnosis) is event free. Two patients are alive after tumor progression: One patient was diagnosed with a medulloblastoma, and one patient was diagnosed with an osteosarcoma as second malignancies. A control group extracted from the Surveillance, Epidemiology, and End Results data had lower survival rates: the difference between the groups was not statistically significant (P = 0.26).
  
  
  CONCLUSIONS
  This chemotherapy will not be used in a randomized trial of patients with glioblastoma; however, it may be evaluated for patients with tumors that have more chemoresponsive histologies.
authors.affiliation: University of Calgary, c/o Alberta Children's Hospital, Alberta, Canada. johannes.wolff@crhahealth.ab.ca
authors.forename: J E
authors.initials: JE
authors.lastname: Wolff
authors.forename: G
authors.initials: G
authors.lastname: Mölenkamp
authors.forename: S
authors.initials: S
authors.lastname: Westphal
authors.forename: T
authors.initials: T
authors.lastname: Pietsch
authors.forename: A
authors.initials: A
authors.lastname: Gnekow
authors.forename: R D
authors.initials: RD
authors.lastname: Kortmann
authors.forename: J
authors.initials: J
authors.lastname: Kuehl
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011182:Postoperative Care; D015173:Supratentorial Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; C003726:trofosfamide