Combined cyclotron fast-neutron and BCNU therapy in a rat brain-tumor model

The combination of cyclotron fast-neutron radiotherapy with BCNU chemotherapy was compared to 137Cs gamma photon radiotherapy combined with BCNU in the 36B-10, F-344 rat-transplanted glioma model. Radiation and drug treatments were administered 7 to 8 days after intracerebral tumor implantation. Increase in animal survival time was used as the measure of the effectiveness of various treatment schedules. Single-dose neutron or gamma radiotherapy was tested on Day 7 over the ranges 0 to 900 rads and 0 to 2000 rads, respectively. This therapy produced increases in mean survival times up to 70% at the highest radiation doses. When BCNU (10 mg/kg body weight) was administered intravenously on Day 8, 1 day following radiotherapy, mean survival times were increased by an additional 35% to 50%, irrespective of the dose or type of irradiation. In contrast, by using the same radiation and drug doses but scheduling combined therapy trials so that BCNU was administered 1 hour before either neutron or gamma irradiation on Day 7, there was enhancement of the radiation effect by BCNU. Under these conditions, the maximum enhancement of the mean survival time was 70% to 75% in neutron-treated animals and 120% to 150% in gamma-treated animals. Treatment with BCNU 1 hour before or 1 day after neutron irradiation proved to be no more effective in proving the survival time of tumor-bearing animals than the drug similarly combined with conventional gamma irradiation.