Treatment schedule of combination using radiation and ACNU in the experimental brain tumors

Abstract

This study was undertaken to identify the combined effect of ACNU treatment and irradiation in a rat brain tumor model. The brain tumor model was produced in CDF male rats by stereotaxic inoculation of F-98 or D-74 glioma clone cells. In the first series using F-98, the median survival time of the controls was 38 days. ACNU alone (7 mg/kg×3) on Day 5, 6, and 7 following tumor cell inoculation resulted in 45 days (P<0.001), a single dose of irradiation alone (1, 500 rads) on Day 8 produced 45 days (P<0.001) and the combined treatment resulted in 58 days with a 28.9% increased life span (%ILS), which was significantly longer than that of the irradiation alone (P = 0.0068). In the second series using D-74, the median survival time of the control group was 20 days. ACNU alone (7 mg/kg×3) showed no significant increase in survival time. A single dose of irradiation resulted in 23 days (P<0.001) and the combined treatment in 26 days with 13.0% ILS, significantly longer than that of irradiation alone (P<0.001). The third series assessed the schedule dependence of the combined treatment effects of ACNU and irradiation using D-74. The median survival time of the controls was 21 days. A single dose of ACNU (20 mg/kg) produced no significant increase. Irradiation alone (1, 500 rads) on Day 8 resulted in 26 days (P<0.001). A combined treatment group receiving ACNU 1 hour prior to irradiation showed a significant increase (31 days with 19.2% ILS) and this was significantly longer than that of irradiation alone (P<0.001). A significant increase in survival time was also observed (P=0.0060) when ACNU was administered three days prior to irradiation (28.5 days with 9.6% ILS). Although an increase in survival time was also observed when ACNU was given 26 or 6 hours prior to irradiation as well as 6 hours following irradiation, survival times after such combined treatments were not significantly longer than those of irradiation alone. No significant difference in tumor size at the time of death was noted among any of the groups. In conclusion, combined treatment with ACNU and irradiation may have a synergistic effect on the rat brain tumor model, and this effect depends on the combination schedule.