[Combination therapy with HU IFN-beta and ACNU against malignant brain tumors, Part 1. Experimental study in vitro]

Augmentation of cytotoxicity against malignant glioma using a combination of Hu IFN-beta and ACNU was analyzed in vitro from the points of cell growth inhibition and alteration of the DNA histogram. Cytotoxicity was tested by exposing 13 human glioma cell lines to ACNU at a concentration of 5 micrograms/ml and/or Hu IFN-beta at a concentration of 10(3) IU/microliters. These concentrations were considered to be clinical doses. Additive or synergistic effects of the combination of the two agents were observed in all cell lines tested. The cytotoxic effect of two log kill was seen in two cell lines given ACNU treatment alone, one cell line treated with Hu IFN-beta alone, and nine treated with the combination. Flow-cytometry studies of the DNA histogram showed accumulation in the G2+M phase with ACNU and in the S phase with Hu IFN-beta. On the other hand, marked accumulation using the combination in the S phase followed by the G2+M phase was observed and this accumulation lasted for over a week. The present results show an augmentation of antitumor activity and suggest the effectiveness of combined Hu IFN-beta/ACNU therapy in the treatment of patients with malignant glioma.