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

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Abstract
The combination of cyclotron fast-neutron radiotherapy with BCNU [1,3-bis-(2-chloroethyl)-1-nitrosourea] 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 7-8 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 0-900 rads and 0-2000 rads, respectively. This therapy produced increases in mean survival time up to 70% at the highest radiation doses. When BCNU (10 mg/kg body wt) was administered i.v. on day 8, 1 day following radiotherapy, mean survival times were increased by an additional 35%-50%, irrespective of the dose or type of irradiation. By using the same radiation and drug doses but scheduling combined therapy trials so that BCNU was administered 1 h before 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 70-75% in neutron-treated animals and 120-150% in .gamma.-treated animals. Treatment with BCNU 1 h before or 1 day after neutron irradiation was no more effective in improving the survival time of tumor-bearing animals than the drug similarly combined with conventional .gamma.-irradiation.

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