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  • Title: In vivo antitumor effects of fluoropyrimidines on colon adenocarcinoma 38 and enhancement by leucovorin.
    Author: Iigo M, Nishikata K, Hoshi A.
    Journal: Jpn J Cancer Res; 1992 Apr; 83(4):392-6. PubMed ID: 1387127.
    Abstract:
    Antitumor effect and active metabolites of fluoropyrimidines were examined in mice with transplantable colon adenocarcinoma 38 (Co 38). 5-Fluoro-2'-deoxyuridine (FUdR) treatment resulted in a much higher level of free 5-fluoro-2'-deoxyuridine-5'-monophosphate in the tumor than 5-fluorouracil (5-FU) did, and thymidylate synthase was almost completely inhibited after FUdR treatment, but FUdR showed weaker antitumor activity than 5-FU did. Moreover, 5-fluorouridine (FUR) also hardly inhibited tumor growth. A more marked tumor inhibition was obtained when FUdR and FUR were administered together. The antitumor activity of 5-FU was similar to that of the combination of FUdR and FUR. In combination with 2,2'-anhydro-5-ethyluridine, a uridine phosphorylase inhibitor, FUdR lost its antitumor activity, but that of FUR was somewhat potentiated. On the other hand, in combination with leucovorin (LV), 5-FU showed markedly potentiated antitumor activity, while the antitumor activity of FUdR or FUR was not potentiated. Addition of LV to the combination of FUdR and FUR enhanced the inhibitory effect of the drugs. From these results, the combination of FUdR and FUR together with LV, and the combination of 5-FU and LV seem to be highly efficacious against Co 38.
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