The combined-action of ici-d1694, 5-fluoro-2'-deoxyuridine and 5-Fluorouracil in inhibiting the growth of a human renal-cell carcinoma cell-line (rpmi-se) in-vitro.

: In order to investigate possible interactions among ICI-D1694 (a new folate-analog thymidylate synthase inhibitor), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-fluorouracil (FUra), the effect of these agents alone and in 2-drug combinations against a human renal cell carcinoma cell line (RPMI-SE) in vitro was investigated. The median IC50's for cell growth inhibition for ICI-D1694, FdUrd and FUra were 4.00, 7.23 and 1,340 nM, respectively. To quantitatively assess the degree of agent-combined action for 2-agent combinations of the 3 drugs, data from combination experiments were fitted with a response surface mathematical model (Greco et al, Cancer Res 50: 5318-5327, 1990). In 3 experiments for each combination, moderate Loewe synergism was consistently shown for ICI-D1694/FdUrd, less prominent Loewe synergism was indicated for FdUrd/FUra; and Loewe additivity was shown for ICI-D1694/FUra. Studies in vitro to elucidate the mechanism of the interaction of ICI-D1694 + FdURD, and in vivo to establish possible therapeutic advantages are warranted.