Antitumor effect and tumor level of 5-fluoro-2'-deoxyuridylate following oral administration of tetradecyl 2'-deoxy-5-fluoro-5'-uridylate.

The antitumor effect and tumor levels of 5-fluoro-2'-deoxyuridylate (FdUMP) following oral administration of tetradecyl 2'-deoxy-5-fluoro-5'-uridylate (TT-62) were compared with those attained following intravenous (i.v.) or intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU) or 5-fluoro-2'-deoxyuridine (FUdR) in BDF1 mice bearing murine mammary adenocarcinoma 755 and athymic mice bearing the transplantable human colon adenocarcinoma LS174T. Oral administration of TT-62 showed a stronger antitumor effect against adenocarcinoma 755 than FUdR. The maximum effect of TT-62 was similar to that of 5-FU. However, TT-62 and FUdR treatments were more effective than i.v. administration of 5-FU against LS174T. Thus, oral administration of TT-62 showed marked antitumor activity in both tumor systems. The maximum tolerated dose of FUdR resulted in a much higher level of free FdUMP in the LS174T tumor than that obtained with 5-FU. After oral administration of TT-62 the levels of FdUMP in the tumor were about 10 times those attained with 5-FU, but significantly lower than the levels obtained following i.v. administration of FUdR. With TT-62 the levels of FdUMP in the tumor reached their peak at 60 min following the administration and gradually decreased thereafter. However, FdUMP levels after administration of FUdR decreased rapidly. Three hours after the administration of TT-62 and for up to 24 h the FdUMP levels in the LS174T tumor were almost the same as after administration of FUdR, i.e. effective levels of FdUMP were maintained for a long time with TT-62.