Multiple daily fractionated radiation therapy and misonidazole in the management of malignant astrocytoma. A preliminary report

Abstract

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.

Increasing radiation dose intensity using hyperfractionation in patients with malignant glioma

“…As previously reported [18,19] there was no difference in time to tumor progression or survival between patients on the 6141cGy arm who received misonidazole and those who did not. Therefore, these patients are grouped together in this report.…”

A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma

“…In general, no improvement in survival over conventional treatment was seen. In one study a significant advantage to multiple daily fractions was reported (Shin et al, 1985) but the MST in the control group was only 27 weeks, placing the overall conclusion in some doubt.…”

Modified optimal fractionation for poor prognosis malignant gliomas: An elusive search

“…To confirm the trend seen in their previous trial, Shin [29] et al initiated a larger trial of accelerated RT. A total of 124 patients with malignant glioma were randomized to either conventional fractionated RT (40 Gy/20 fractions in 4 weeks to the whole brain with 2 Gy /fraction, followed by a local tumor boost of 20 Gy/10 fractions/2 weeks); or accelerated RT whereby the patients received 0.89 Gy/fraction; 3 fractions/day as whole-brain radiotherapy (WBRT) to a dose of 50.7 Gy/54 fractions in 3.5 weeks followed by a local tumor boost of 10 Gy/5 fractions in 1 week; or to accelerated RT as above plus misonidazole 1.25 gm/m 2 thrice weekly during the first three weeks of radiotherapy.…”

“…The seven randomized studies (Table II) however are not consistent with each other, with the four larger trials [26,27,32,33] reporting no benefit and the two smaller ones [28,31] showing a trend towards improved survival with acceleration over conventional fractionation. Only one study, by Shin et al [29] reported a survival benefit with accelerated RT. However, the number of patients in their study was small (124 patients only) and only the preliminary results were published.…”