Influence of fractionation schedules on the response of a rat brain tumor to therapy with BCNU and radiation

The maximum dose of 1, 3 bis(2-chloroethyl)-1-nitrosourea (BCNU) that produced minimal toxicity after intraperitoneal administration 2, 3, or 5x/wk for 2 weeks was found to be 3.0, 2.5, or 2.0 mg/kg/treatment, respectively. BCNU toxicity appeared to be related to the total dose administered, which indicated little if any split-dose recovery. Deaths after whole brain irradiation resulted predominantly from starvation because of the inability of the irradiated rats to eat food pellets. When placed on a diet of soft mash, virtually all rats survived irradiation schedules of 520 rad/day 2x/wk for 2 wk; 433 rad/day 3x/wk for 2 wk; and 260 rad/day 5x/wk for 2 wk. There was no additional toxicity when these maximum doses of BCNU and radiation were combined in 2 week fractionation schemes. The 2x/wk and 3x/wk BCNU + radiation schedules, which employed the maximum tolerable doses of each agent, were as effective as the 5x/wk combination schedule in treating day 12 intracerebral 9L brain tumors