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: J E Wolff, G Mölenkamp, S Westphal, T Pietsch, A Gnekow, R D Kortmann, J Kuehl
• Journal: Cancer (Cancer) Vol. 89 Issue 10 Pg. 2131-7 (Nov 15 2000) ISSN: 0008-543X [Print] United States
• PMID: 11066055 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 American Cancer Society.

Chemical References

• Etoposide
• Cyclophosphamide
• trofosfamide

Topics

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