5-Fluorouracil infusions and fractionated doses of radiation: studies with a murine squamous cell carcinoma
Abstract
The present investigation describes the effects on a murine squamous cell tumor of combined treatment using radiation and 5-Fluorouracil (5FU), with emphasis on 5FU infusions. The tumor, SCC VII/To, was grown intramuscularly in the hind legs of C3H mice. Radiation was given locally with 100 kVp X rays either alone or in combination with 5FU by i.p. bolus injections or 4-14 day infusions using subcutaneously implanted mini-osmotic pumps. Studies with radiation alone indicated regrowth delay increased with total dose. This increase was less for fractionated than single doses. The effects of 5FU alone were compared using i.p. injections or 4, 7 or 14 day infusions. Tumor response to single i.p. bolus injections or 4 day infusions were not significantly different. Up to total drug doses of 200 mg/kg, 14 day infusions were least effective on regrowth delay, 4 day infusions were intermediate and 7 day infusions were most effective. Above total drug doses of 200 mg/kg, effects of 14 day infusions on regrowth delay increased rapidly. The LD50 for single i.p. bolus injections and 7 day infusions were similar, 230 and a total drug dose of 270 mg/kg, respectively. When a 7 day infusion of 5FU (133 mg/kg) was combined with increasing total radiation doses (1 or 5 fractions), the increase in regrowth delay was additive. Combining a fractionated dose of 5 Gy per day for 5 days (5/5 Gy) with increasing total drug doses of 5FU (single i.p. bolus injections or 4, 7 or 14 day infusions)…
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