Solid tumor models for the assessment of different treatment modalities. XII. Combined chemotherapy-radiotherapy: variation of time interval between time of administration of 5-fluorouracil and radiation and its effect on the control of tumor growth.

Abstract

The combined effects of radiation and 5-fluorouracil (5-FU) on control of tumor growth rates in the experimental solid tumor 3924A have been determined when radiation (1500 rads) was given 14, 7, 4, 2, 1 and 0.5 days before 5-FU (150 mg/kg); and 1, 2, 4, 7, 11, and 15 days after 5-FU. These results were compared to single doses of each modality given alone and both modalities given simultaneously. Two methods of evaluation were utilized, tumor growth delay and “overall treatment efficiency.” The widely used method of tumor growth delay indicates that the combined effect of radiation and 5-FU significantly increased tumor growth delay over the additive effect of the two modalities given independently for schedules in which radiation was given from 4 days prior to 2 days after 5-FU. Maximum tumor growth delay occurred when radiation was given 4 days before 5-FU; being 2.5 times the additive effects of each modality. Separation of the administration of radiation and 5-FU by ± 7 to 14 days resulted in two distinct perturbations in tumor growth curves and was less effective than when the two agents were given at shorter intervals. The term “overall treatment efficiency”(OTE) has been introduced to determine the magnitude of tumor volume changes following treatment. The OTE indicates that maximum tumor volume reduction also occurred when radiation was given 4 days before 5-FU. OTE was 1.5 times the additive effect of the two modalities given independently at this time. Radiation given 4 days after 5-FU gave less than additive responses, with tumor growth delay and OTE for this combination of 5-FU and radiation being 0.8 and 0.6 of the additive effects, respectively. The effects of combining radiation with 5-FU did not reduce animal survival below the survival level of the group given 5-FU alone in 8 of 10 groups evaluated. Cancer 44:437-445, 1979.