Preradiation chemotherapy for pediatric patients with high-grade glioma.

Abstract

To evaluate the feasibility and efficacy of intensive chemotherapy given prior to irradiation in pediatric patients with malignant glioma, the Society of Pediatric Oncology in Germany started a randomized trial in 1991. The high-grade glioma strata had to be closed because of insufficient patient accrual. The follow-up data from these patients are reported. Fifty-two patients with World Health Organization (WHO) Grade 4 malignant glioma (n = 27 patients) or with WHO Grade 3 anaplastic astrocytoma (n = 25 patients) between the ages of 3 years and 17 years were available for analysis. The tumor locations were supratentorial in 42 patients, the cerebellum in 8 patients, and the spinal cord in 2 patients (the brainstem was excluded). Tumor surgeries were biopsy in 10 patients, partial resection in 5 patients, subtotal resection in 10 patients, and macroscopic total resection in 21 patients. Patients received either 54 grays of irradiation (n = 22 patients) followed by chemotherapy with lomustine, vincristine, and cisplatin (maintenance chemotherapy) or sandwich chemotherapy (n = 30 patients), which consisted of ifosfamide, etoposide, methotrexate, cisplatin, and cytosine arabinoside followed by irradiation. The extent of resection was the most important prognostic factor. The median survival was 5.2 years for patients who underwent tumor resection of > or = 90% compared with 1.3 years for patients who underwent less than complete resection (P < 0.0005). After undergoing macroscopic total resection, sandwich chemotherapy (n = 15 patients) resulted in better overall survival (median, 5.2 years) compared with the maintenance protocol (n = 16 patients; median survival, 1.9 years; P = 0.015). A Cox multivariate regression analysis showed better survival for female patients (P = 0.025), WHO Grade 3 disease (P = 0.016), tumor resection of > or = 90% (P = 0.003), irradiation with > or = 54 grays (P = 0.003), and sandwich chemotherapy (P = 0.006). These data suggest that early, intensive chemotherapy increases survival rates in patients with malignant glioma who undergo complete resection.