Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme

BACKGROUND. Glioblastoma multiforme in childhood is rare, and the prognosis for patients with the disease is poor. The Pediatric Oncology Society of t he Germanic language group (GPOH) enrolls patients in a series of pilot tri als, the first of which is reported here (HIT-GBM-A). METHODS. Twenty-two patients with glioblastoma multiforme, World Health Org anization Grade 4, between the ages of 3-15 years (45% male) were enrolled during the period 1995-1997. There were 13 supratentorial tumors, 8 brainst em tumors, and 1 cerebellar tumor. The patients underwent the following pro cedures: stereotactic biopsy (n = 3 patients), open biopsy (n = 1 patient), partial resection (n = 6 patients), subtotal resection (n = 4 patients), a nd macroscopic total resection (n = 8 patients). Adjuvant treatment consist ed of oral chemotherapy with trofosfamide, 100 mg/m(2), and etoposide, 25 m g/m(2), daily or for 21-day cycles interrupted by 1-week rests. Standard fr actionated radiation (54 grays) was started concurrently with the first cyc le. RESULTS. The chemotherapy was well tolerated, with no treatment-related dea ths and only minor side effects. The responses in 12 evaluable patients aft er two cycles were as follows: 1 complete response, 1 partial response, 3 p atients with stable disease, and 7 patients with progressive disease. The m edian overall survival was 12 months. The 1-year, 2-year, and 4-year overal l survival rates were 52%, 26%, and 22%, respectively, and the event free s urvival rates were 26%, 22%, and 4%, respectively. None of the four survivi ng patients (3.2 years, 3.4 years, 3.0 years, and 4.2 years after diagnosis ) is event free. Two patients are alive after tumor progression: One patien t 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 pa tients with glioblastoma; however, it may be evaluated for patients with tu mors that have more chemoresponsive histologies. (C) 2000 American Cancer S ociety.