EFFECT OF TIME BETWEEN X-IRRADIATION AND CHEMOTHERAPY ON THE GROWTH OF 3 SOLID MOUSE-TUMORS .6. BCNU

Experiments have been carried out to determine the effect of different time intervals between the administration of X-irradiation (1200 rad) and BCNU (15 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered by the intraperitoneal route either 24, 6, or 2 hr before radiation. All irradiations were carried out in unanesthetized mice. The growth delays due to the drug alone were 2, 6, and 11 days for the RIF-1, EMT6, and KHT tumors, respectively. No consistent general pattern emerged from the results of combination treatments. For the RIF-1 tumor, the growth delays following combination treatments were generally less than predicted by the simple addition of the growth delays for the single modalities. For EMT6 this was true when BCNU was administered immediately before X-rays, but not for other timings. In the KHT tumor an unexpectedly high incidence of long-term tumor controls was seen in the group which received BCNU at 2 hr before X-rays. In addition to the single dose studies (above), fractionated regimens in which radiation and BCNU were combined in several different ways were tested with the RIF-1 tumor. None of the combination schedules tested showed a greater-than-additive effect. © 1979.