Efficacy of post operative adjuvant therapy with human interferon beta, MCNU and radiation (IMR) for malignant glioma: comparison among three protocols.

In order to develop ultimate adjuvant therapy for malignant gliomas, we analysed 77 patients with malignant gliomas (29 anaplastic astrocytomas (AAs) and 48 glioblastoma multiformes (GMs)) treated by three protocols of IMR therapy (human interferon-beta (HuIFN-beta), MCNU and radiation). In protocol 1 (n = 45: AA = 13, GM = 32), 1 x 10(6) IU of HuIFN-beta was administrated intravenously once a day for 7 days. On day 2, MCNU was administrated at a dose of 2 mg/kg b.w. intravenously and from day 3, radiation was started in five weekly fractions of 2 Gy for 6 weeks. Total dose was 60 Gy. Protocol 2 (n = 19: AA = 11, GM = 8) was comparable with protocol 1 except HuIFN-beta was administrated twice a day at a dose of 1 x 10(6) IU each. Protocol 3 (n = 13: AA = 5, GM = 8) differed from protocol 2 only in a high dose-hyperfractionated radiation which was given twice a day at a dose of 1.5 Gy each and for a total dose of 66 Gy. Antitumor effects were evaluated by survival and response rate determined by decrease of tumor size. Significant improvement was obtained in patients with AAs by protocol 2 and 3. Response rates of patients with AAs and GMs were 46.2% and 50% in protocol 1, 63.6% and 50% in protocol 2, and 80% and 50% in protocol 3, respectively. One and two year survival rates in AAs were 46.4% and 34.8% in protocol 1, both 75% in protocol 2, and both 100% in protocol 3. Survival rates in GMs were not different among them. Except of radiation necrosis, which was observed in 38.5% of the patients under protocol 3, there was no significant difference in the adverse effects among the three protocols. In the present study, the efficacy of IMR therapy for patients with malignant gliomas, especially for AAs, was cofirmed. We conclude that twice a day administrations of HuIFN-beta in combination with a high dose-hyperfractionated radiation provide increased efficacy in IMR therapy.