Toxicity And Antitumor Effect Of 5-Fluorouracil (Fu) 157 And Its Rescue By Uridine (Ur): 157 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1985-07

AUTHORS

G J Peters, J Van Dijk, C Van Groeninqen, E J Laurensse, A Leyva, J Lankelma, H M Pinedo

ABSTRACT

The application of FU in the treatment of colon cancer is limited because of myeloid and gastrointestinal toxicity. It has been demonstrated that UR is able to rescue mice from the toxic effects of FU, which precludes the use of higher FU doses. Antitumor effect and toxicity were studied in two murine colon carcinomas, both sensitive and resistant, which also show marked differences in FU metabolism (e.g. uridine phosphorylase is 10 times higher in Colon 26 than in Colon 38). Mice received FU weekly. Colon 38, grown in C57B1 mice, was sensitive to FU; at 100 mg/FU kg 70% of the tumors disappeared. UR administration (3500 mg/kg) after 2 and 20 hr, decreased the number of complete responders. Colon 26, grown in Balb/c mice, was not sensitive to 100 mg FU/kg. FU was lethal at 300 mg/kg, but UR increased the life-span, while a significant tumor growth delay was observed. 100 mg FU/kg caused a severe leucopenia which reached a nadir of 10% after the second dose. UR administration prevented this leucopenia and a faster recovery was observed. UR was not lethal, although, a sharp fall in body temperature was observed after 1 hr (± 10°C). However, this hypothermia was not observed with patients in a Phase I trial with UR. In conclusion: hematological toxicity caused by FU can be prevented by delayed administration of UR; the antitumor activity seems to be affected, but this was not significant; the side-effects of UR seem to be acceptable to proceed Phase I trials. More... »

PAGES

770

Identifiers

URI

http://scigraph.springernature.com/pub.10.1203/00006450-198507000-00177

DOI

http://dx.doi.org/10.1203/00006450-198507000-00177

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029720790


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