Solid tumor models for the assessment of different treatment modalities. XIX. Tumor cure rates and tumor control following sequential administration of radiation and cyclophosphamide

Abstract

Tumor cure rates .gtoreq. 50% were realized by the administration of 3 and 4 series of 1500 rads radiation and 150 mg/kg (0.9 g/m2) cyclophosphamide [to rats bearing hepatoma 3924A] which were separated by 1, 7 or 11 days. Increasing the time between treatment modalities from 1 to 7 and 11 days provided a 2- to 3-wk recovery period for each treatment modality without a reduction in cure rates. However, the mean time for complete response increased from 24.8 .+-. 17 days for 1 day, 30.7 .+-. 3.0 days for 7 days, and 38.3 .+-. 4.8 days for 11 days between treatment modalities. Giving the 2nd series of radiation and cyclophosphamide on days 6 and 17 resulted in a cure rate of 50%. Increasing this interval to 21-22 days resulted in no cures. The results of giving each modality alone at 11-day intervals were compared with results of alternating administration of the 2 modalities at 11-day intervals. Comparing the 3 regimens where a treatment was given every 11 days, the numbers of animals with cures were 0 of 10 for cyclophosphamide alone, 2 of 10 for radiation alone, and 5 of 9 for alternation of the 2 treatments every 11 days. Well-defined periods of acclerated growth occur between 10 and 20 days after administration of single doses of either radiation or cyclophosphamide. The increased effectiveness of alternate utilization of the 2 modalities suggests that prior treatment by 1 modality increases tumor sensitivity to the 2nd modality.