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Solid tumor models for the assessment of different treatment modalities 2. combined chemo therapy radio therapy variation of time interval between time of administration of 5 fluoro uracil and radiation and its effect on the control of tumor growth



Solid tumor models for the assessment of different treatment modalities 2. combined chemo therapy radio therapy variation of time interval between time of administration of 5 fluoro uracil and radiation and its effect on the control of tumor growth



Cancer 44(2): 437-445



The combined effects of radiation and 5-fluorouracil (5-FU) on control of tumor growth rates in the experimental solid tumor 3924A [rat hepatoma] were 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. Methods of evaluation (2) 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 2 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 2 distinct perturbations in tumor growth curves and was less effective than when the 2 agents were given at shorter intervals. The term overall treatment efficiency (OTE) was 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 2 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 8/10 groups evaluated.

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