Inhibition of murine colon adenocarcinomas and Lewis lung carcinoma by 1-hexylcarbamoyl-5-fluorouracil

Abstract

1-Hexylcarbamoyl-5-fluorouracil (HCFU) and its parent compound 5-fluorouracil (5-FU) were tested PO for antitumor activity against mouse colon adenocarcinoma 26 (colon 26), colon adenocarcinoma 38 (colon 38), and Lewis lung carcinoma. The drugs were given orally at 2--4 days intervals for a total of ten doses. 5-FU was moderately active against colons 26 and 38 but not against Lewis lung carcinoma. In this treatment regimen the most impressive antitumor activity was obtained with HCFU against colons 26 and 38, especially colon 38 tumor. At 300 mg HCFU/kg, one out of seven mice inoculated with colon 26 and five out of ten mice inoculated with colon 38 became tumor-free. HCFU, however, was marginally effective in the prolongation of survival time of mice bearing Lewis lung carcinoma. 5-FU is approximately twice as active as HCFU against cultured cell lines from colon 26, colon 38, and Lewis lung carcinoma. Lewis lung carcinoma cells were most sensitive against HCFU, which is in contrast to the results obtained in the in vivo experiment. The IC50 value of HCFU against Lewis lung carcinoma cells was approximately half that against colon 26 and colon 38 cells. This higher sensitivity of Lewis lung cells against HCFU could be explained by the higher cellular uptake of the drug.