Treatment of children with newly diagnosed brain stem gliomas with intravenous recombinant beta-interferon and hyperfractionated radiation therapy: a childrens cancer group phase I/II study.

BACKGROUND: Prognosis for the majority of children with brain stem gliomas is dismal. In previous studies, recombinant beta-interferon (r beta IF) has been shown to be effective for children with recurrent brain stem gliomas and may also act synergistically with radiotherapy (RT).
METHODS: Thirty-two children with diffuse intrinsic brain stem gliomas were treated with (r beta IF) and 7200 centigray (cGy) of hyperfractionated RT (100 cGy twice-daily fractions) to determine the toxicity of treatment and the tolerance of the brain stem to this regimen, as well as to assess survival. Patients were treated with r beta IF 3 times per week during RT and then for 8 weeks following RT. Initially, a dose escalation trial was performed.
RESULTS: Interferon was initially begun at 12.5 x 10(6) IU/m2 and escalated up to 400 x 10(6) IU/m2. The safe starting dose was determined to be 100 x 10 (6) IU/m2. Due to unacceptable toxicity, the maintenance dose was reduced to 200 x 10 (6) IU/m2. Therapy was relatively well tolerated, although 13 of the patients required dose modifications due to hepatic or hematologic toxicity. Four of the patients had to discontinue treatment due to this toxicity. One patient died while receiving maintenance IF of encephalopathy, seizures, and brain stem dysfunction; believed possibly due to the r beta IF. Thirty of the 32 patients have developed progressive disease. The median time to progression from study entry was five months and the median time to death was 9 months.
CONCLUSIONS: We conclude that r beta IF plus hyperfractionated therapy can be tolerated by children with newly diagnosed brain stem gliomas, although there is occasional dose-limiting hepatic, blood, and central nervous system toxicity. This therapy did not result in a higher rate of disease control.