Misonidazole and irradiation in the treatment of high-grade astrocytomas: further report of the Vienna Study Group.

A randomized study investigating the value of misonidazole in patients irradiated for grade III and IV supratentorial astrocytomas was started in June 1977. With a minimum follow-up time of 6 months, 45 patients who completed therapy are available for analysis. All patients received the same radiation treatment (66.5 Gy in 31 fractions over 7.5 weeks, field size reduction after 45 Gy). In the first, second and eighth week, a 4 Gy tumor dose was given on Monday and Thursday. Misonidazole was given 4 hours before irradiation to 18 randomized patients on those 6 treatment days (2.1-2.7 g/m2 per treatment day). Daily tumor doses of 1.7 Gy were administered Monday through Friday from the third until the seventh week. Median survival for patients treated with misonidazole is 13.8 months; for those treated by irradiation alone it was 9.8 months. The corresponding 1 year survival rates are 64 and 25%, respectively. Survival plots indicate some advantage for the patients treated with misonidazole, however statistically there is no significant difference observed (p greater than 0.08). There are no significant differences in Karnofsky performance status, sex and in histological grade or in age distribution between the groups. However, the type of surgery (complete or subtotal) influenced survival markedly: patients with complete surgery lived significantly longer (p less than 0.0009). Neurotoxic side effects of misonidazole were minimal.