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 f olate-analog thymidylate synthase inhibitor), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-fluorouracil (FUra), the effect of these agents alone a nd in 2-drug combinations against a human renal cell carcinoma cell li ne (RPMI-SE) in vitro was investigated. The median IC50's for cell gro wth inhibition for ICI-D1694, FdUrd and FUra were 4.00, 7.23 and 1,340 nM, respectively. To quantitatively assess the degree of agent-combin ed action for 2-agent combinations of the 3 drugs, data from combinati on experiments were fitted with a response surface mathematical model (Greco et al, Cancer Res 50: 5318-5327, 1990). In 3 experiments for ea ch combination, moderate Loewe synergism was consistently shown for IC I-D1694/FdUrd, less prominent Loewe synergism was indicated for FdUrd/ FUra; and Loewe additivity was shown for ICI-D1694/FUra. Studies in vi tro to elucidate the mechanism of the interaction of ICI-D1694 + FdURD , and in vivo to establish possible therapeutic advantages are warrant ed.