Growth delay in a murine squamous cell tumor after local radiation and concurrent infusional 5-fluorouracil treatment

In an effort to increase local control rates in a variety of human squamous cell carcinomas, infusional 5-Fluorouracil (5FU) has been combined with conventional fractionated radiation. The present work uses an experimental tumor system to examine the interactive effect of radiation and 5FU treatment. A transplantable murine tumor of squamous cell origin, SCC VII/SF, was grown in the legs of C3H mice. Leg diameter was measured and converted to tumor weight by an empirical calibration curve. Tumors of 0.3 g were treated by local irradiation with single or fractionated doses of 100 kVp X rays, alone, or in combination with a 7 day infusion of 5FU delivered by subcutaneously implanted mini-osmotic pumps. The tumor response was measured for single doses of 10-30 Gy and a fractionated dose of 5 Gy per day for 5 days. Studies done with single doses of radiation indicated delay and extent of tumor volume reduction, increased with dose. The effects of 5FU as a single agent were studied at infusion rates of 0.7, 1.3, or 2 mg/kg/hr for seven days. The LD50 for 5FU infusion was 1.3 mg/kg/hr. A single dose of 20 Gy or a fractionated dose of 5 Gy per day for 5 days was compared both in the presence and absence of 5FU at 0.7 mg/kg/hr. Results were consistent with the single dose radiation and infusional 5FU, interacting in a less than simply additive fashion, whereas, the 5FU-fractionated radiation interaction appears to be greater than simply additive. These results suggest that infusional 5FU may be enhancing the effects of fractionated radiation by inhibiting tumor cell repair and/or repopulation.