TREATMENT OF CHILDREN WITH NEWLY-DIAGNOSED BRAIN-STEM GLIOMAS WITH INTRAVENOUS RECOMBINANT INTERFERON-BETA AND HYPERFRACTIONATED RADIATION-THERAPY - A CHILDRENS CANCER GROUP PHASE I II STUDY/

BACKGROUND. Prognosis for the majority of children with brain stem gli omas is dismal. In previous studies, recombinant beta-interferon (r be ta IF) has been shown to be effective for children with recurrent brai n stem gliomas and may also act synergistically with radiotherapy (RT) . METHODS. Thirty-two children with diffuse intrinsic brain stem gliom as were treated with (r beta IF) and 7200 centigray (cGy) of hyperfrac tionated RT (100 cGy twice-daily fractions) to determine the toxicity of treatment and the tolerance of the brain stem to this regimen, as w ell as to assess survival. Patients were treated with r beta IF 3 time s per week during RT and then for 8 weeks following RT. Initially, a d ose escalation trial was performed. RESULTS. Interferon was initially begun at 12.5 X 10(6) IU/m(2) and escalated up to 400 x 10(6) IU/m(2). The safe starting dose was determined to be 100 x 10(6) IU/m(2). Due to unacceptable toxicity, the maintenance dose was reduced to 200 x 10 (6) IU/ m(2). Therapy was relatively well tolerated, although 13 of th e patients required dose modifications due to hepatic or hematologic t oxicity. Four of the patients had to discontinue treatment due to this toxicity. One patient died while receiving maintenance IF of encephal opathy, seizures, and brain stem dysfunction; believed possibly due to the r beta IF. Thirty of the 32 patients have developed progressive d isease. The median time to progression from study entry was five month s and the median time to death was 9 months. CONCLUSIONS. We conclude that r beta IF plus hyperfractionated therapy can be tolerated by chil dren with newly diagnosed brain stem gliomas, although there is occasi onal dose-limiting hepatic, blood, and central nervous system toxicity . This therapy did not result in a higher rate of disease control. (C) 1996 American Cancer Society.