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Summary.-As a continuation of a previous controlled trial using "high-dose" metronidazole as a specific sensitizer of hypoxic cells, we used a more efficient nitroimidazole derivative (misonidazole, MISO) in combination with higher doses of radiation in patients with supratentorial high-grade astrocytomas. Sixty-six patients were stratified according to functional level and histological grading, and randomly allocated within 2 weeks of operation to 1 of 3 therapeutic groups: 1, conventional radiation alone; 2, large fractions of radiation with high-dose metronidazole; and 3, radiation as in Group 2 but with equitoxic doses of MISO.We examined survival as the principal end-point of the study.Neither by increasing the dose of radiation over the previous study, nor by using a more efficient sensitizer, were we able to improve survival over the current conventional daily fractionated radiation.

Various attempts have been made to improve the effectiveness of radiation in the treatment of cerebral malignant astrocytomas. A trend favoring multiple daily fractionated (MDF) radiation therapy over conventional single daily fractionated (CF) radiation therapy was identified in our previous study. In order to assess the effect of MDF with and without misonidazole, a province-wide prospective randomized trial was initiated in January 1981. By March 1984, 124 patients with histologically verified grade III and IV astrocytomas were randomized to CF (5800 cGy/6 weeks/30 fractions), MDF (6141 cGy/4.5 weeks/69 fractions at 89 cGy every 3-4 hours, three times a day) and MDF in combination with misonidazole (1.25 g/m2 three times weekly for the first 3 weeks). Thirty-eight patients were randomized to CF, 43 patients to MDF, and 43 patients to MDF and misonidazole. At the preliminary assessment in July 1984, the median survival time was 27 weeks for the CF group, 39 weeks for the MDF group and 49 weeks for MDF and misonidazole group. The 1-year actuarial survival rate from surgery was 20% for CF group, 41% for MDF group, and 45% for MDF and misonidazole group. There is a statistically significant difference (P less than 0.001) between the CF and MDF group. However, the addition of misonidazole does not significantly alter survival.

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