To assess the potential hazards of compromised liver function and deficient granulocyte reserves during therapy with 5‐fluorouracil, the metabolism of uracil‐2‐14CO2 and the granulocyte response to a bacterial endotoxin, pyrexal, were studied in cancer patients. An inadequate response to pyrexal was invariably associated with increased toxicity, in terms of leukopenia, during therapy with 5‐fluorouracil. Severe leukopenia also occurred in subjects with normal granulocyte reserves. Other studies showed that in patients either with demonstrable liver metastases or in whom subsequent administration of 5‐fluorouracil produced particularly severe toxicity or toxic manifestations with less than average doses of the drug, the specific activity of expired 14CO2 derived from uracil‐2‐14C was lower than in other patients. The results of the more customary tests of liver function did not correlate closely with these findings. It is suggested, therefore, that the metabolism of uracil to CO2 in con;unction with determinations of the granulocyte response to endotoxin, may serve as a useful index of toxicity which may be anticipated from 5‐fluorouracil.
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Creasey et al. (1967) studied this question.