Combination therapy of a solid murine tumor with cyclophosphamide and radiation: The effects of time,dose and assay method

The combined effects of Cyclophosphamide (CY) and radiation on the EMT6/SF tumor growing subcutaneously in mice were studied using both the growth delay assay and an in vitro assay. When drug was given between 48 hr before and 48 hr after radiation, cyclic variations in response were seen with the in vitro assay, e.g. the response was always greater when drug was given 1 or 8 hr compared with 4 hr after irradiation, Combined CY and radiation using doses which reduced survival to approx. 10% when each agent was given alone (120 mg/kg CY and 800 rad) produced slight potentiation at some time intervals. With the growth delay assay at these doses apparent potentiation was seen but which was probably due to the slower regrowth rate of tumors after combined treatment. No potentiation was seen with either assay when a lower drug dose (50 mg/kg) was used. Potentiation was seen with the growth delay assay, however, when larger doses were used (150 mg/kg CY, 1500 or 2000 rad X-rays), indicating a marked dose dependence for potentiation.