PREIRRADATION CHEMOTHERAPY AND HYPERFRACTIONATED RADIATION-THERAPY 66GY FOR CHILDREN WITH BRAIN-STEM TUMORS - A PHASE-II STUDY OF THE PEDIATRIC-ONCOLOGY-GROUP, PROTOCOL 8833

Background. Fewer than 20% of children with intrinsic brain stem tumor s survive longer than 2 years. Although some improvement has been note d in recent trials using higher doses of hyperfractionated radiation t herapy (HRT), the feasibility of pre-irradiation chemotherapy has not been explored in these patients with poor prognosis. Methods. Between February 1988 and March 1989,37 patients were entered onto a Phase II Pediatric Oncology Group study for evaluating the feasibility, respons e, and toxicity of treating children with high-risk brain stem tumors with chemotherapy followed by HRT (66 Gy). Chemotherapy consisted of f our cycles of cisplatin (100 mg/m2) plus cyclophosphamide (3 g/m2). Re sults. Of 32 eligible patients, 65% improved clinically during the fir st 2-3 cycles of chemotherapy; 75% of those improving were weaned from steroids. On neuroradiology review of scans before and after chemothe rapy, 3 patients had partial responses (PR, > 50% shrinkage), 23 had s table disease (SD), and 6 had progressive disease (PD). The median sur vival was 9 months. The three patients who attained a PR on chemothera py were among the longest survivors at 38 plus, 44 plus, and 40 months . Toxicities included profound but brief marrow suppression, transient electrolyte-renal dysfunction, and ototoxicity. Brain stem swelling f rom intravenous fluids caused transient deterioration in two patients. Six patients developed an unusual syndrome of transient marrow suppre ssion after HRT. Conclusions. This study suggests that pre-irradiation chemotherapy can be successfully added to the treatment of patients w ith brain stem tumors with both clinical and objective responses noted , but that other agents must be identified to overcome the apparent de velopment of drug resistance and to improve survival.