Correlation of the response of recurrent malignant gliomas treated with interferon alpha with tumor interferon alpha...

Malignant gliomas are treated by combining surgery and radiation with chemotherapy. Cure is rare and utilizing information arising from our improved understanding of brain tumor biology may be of value. Interferon alpha (IFNalpha) treatment as restorative immunotherapy has been utilized in malignant gliomas in the past. Interferon alpha/beta gene presence is variable in these tumors. The relationship between response to IFNalpha therapy and gene status has not been assessed prospectively. Patients with recurrent malignant gliomas were treated with 8-week courses of IFNalpha. Clinical and laboratory toxicity was assessed and response determined by MRI scans. Tumor interferon alpha/beta gene content was measured. Toxicities included fourteen grade 3/4 neuro-motor events, and eleven grade 3 neuro-cortical events. Rapid tolerance developed and with dose reductions few doses were missed. Three individuals with glioblastoma multiforme demonstrated a partial response. Median time to progression was 24.6 (+/-17.6) weeks for all glioblastomas. The correlation between longer time to progression and lower tumor IFNalpha gene content as measured here was significant. A minority of patients with recurrent malignant gliomas will respond to IFNalpha therapy at starting doses of 20 Mu/m(2) and above. These doses are associated with significant toxicity. A relationship between the tumor IFNalpha gene status and tumor response to therapy may be present. With current improved understanding of IFNalpha toxicities and ability to measure tumor IFNalpha function, this therapy warrants further evaluation for identifying patients whose tumors are likely to be responsive to IFNalpha therapy.