COMBINATION THERAPY OF A SOLID MURINE TUMOR WITH 1, 3 BIS (2-CHLOROETHYL)-1-NITROSOUREA AND IRRADIATION

The EMT6/SF tumor growing subcutaneously in mice was used to study the combined effects of BCNU and radiation, using both growth delay and in vitro assays. BCNU (15 mg/kg) appeared to potentiate the effect of X-rays (800 rad) when assayed by growth delay, the largest effect occurring when drug was given 1 to 8 hours after irradiation. The regrowth rates of tumors after combined treatment were slower than untreated tumors, but not slower than the X-ray control, and therefore any attempt to correct for the different regrowth rates did not alter the conclusion that potentiation between drug and radiation occurred. Of the 9 drugs studied in our laboratory, BCNU caused the largest amount of cell killing for a given growth delay when assayed in vitro. Consequently a lower drug dose of 7.5 mg/kg, giving a surviving fraction of 10%, was used with the in vitro assay. Cyclic variation in cell survival were seen as the interval between drug and radiation was varied between -48 and +48 hours. Maximum killing occurred when drug was given 1 hr after X-rays but was only slightly greater than expected from additivity. Tumor control (TCD50) experiments on small tumors were also carried out to investigate the effects of high drug and radiation doses. © 1979.