title: 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.
abstract: 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.
authors.affiliation: ROSWELL PK CANC INST,GRACE CANC DRUG CTR,DEPT UROL ONCOL,ELM & CARLTON ST,BUFFALO,NY 14263. ROSWELL PK CANC INST,DEPT EXPTL THERAPEUT,BUFFALO,NY 14263. ROSWELL PK CANC INST,DEPT BIOMATH,BUFFALO,NY 14263. NEW YORK STATE DEPT HLTH,BUFFALO,NY 14263.
authors.forename: M
authors.initials: M
authors.lastname: Guimaraes
authors.forename: W
authors.initials: W
authors.lastname: Greco
authors.forename: H
authors.initials: H
authors.lastname: Slocum
authors.forename: R
authors.initials: R
authors.lastname: Huben
authors.forename: Y
authors.initials: Y
authors.lastname: Rustum