Clinical effect of interferon in malignant brain tumours

Abstract

Phase I and phase II clinical studies of interferon (IFN) were conducted in malignant brain tumours (47 cases of glioblastoma, medulloblastoma and others) using three preparations of the drug. The drug was administered daily in doses 3.0 − 9.0 × 10⁶ I.U. locally or intravenously (β-type) or intramuscularly (α-type). The administration was continued as many days as possible, eight weeks being the shortest period. The efficacy of the therapy was assessed mainly by the CT findings (computed volume of the tumour). As for efficacy against glioblastomas, the highest effectiveness rate (40%) was obtained with Human Fibroblast IFN (HFIF) (β-type) (Toray) (one case of complete remission and seven cases of partial remission out of 20 cases) as compared to Human Lymphoblastoid IFN (HLBI) (αa-type) (Wellcome) (one case of partial remission out of three cases) and recombinant IFN (rIFN-αA) (α-type) (Roche) (two cases of partial remission out of nine cases). The high rate of responsiveness of HFIF seems to be largely attributable to the local, rather than systemic, administration of the drug. Our pharmacokinetic study revealed that, by means of intrathecal administration a much higher IFN titre was detected in the cerebrospinal fluid, while by intravenous or intramuscular route, the IFN titre in the CSF was undetectably low. The generally lower incidence of side-effects with HFIF compared to other preparations was also largely ascribable to the route of administration. IFN therapy in combination with radiotherapy and/or chemotherapy should also be investigated.