Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme

Cancer. 2000 Nov 15;89(10):2131-7. doi: 10.1002/1097-0142(20001115)89:10<2131::aid-cncr14>3.0.co;2-j.

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Stem Neoplasms / drug therapy*
  • Brain Stem Neoplasms / mortality
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / analogs & derivatives
  • Cyclophosphamide / therapeutic use*
  • Etoposide / administration & dosage
  • Etoposide / therapeutic use*
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Humans
  • Male
  • Pilot Projects
  • Postoperative Care
  • Supratentorial Neoplasms / drug therapy*
  • Supratentorial Neoplasms / mortality
  • Survival Analysis
  • Treatment Outcome

Substances

  • Etoposide
  • Cyclophosphamide
  • trofosfamide