Summary
The present study was designed to analyse the cytotoxic effects of the combination of fotemustine with 5-fluorouracil (5-FU) plus folinic acid (FA). Two human tumor cell lines were used; one line was derived from colon cancer (WIDR) and the other, from a non-small-cell lung cancer (CAL 12). Cytotoxic effects were assessed using the MTT (tetrazolium bromide) semi-automated test in 96-well incubation plates. The effects of various drug combinations were evaluated by the isobologram method. The drug combinations tested included fotemustine concentrations of 20, 30, 40, 50 and 70 μg/ml. 5-FU concentrations of 5, 15 and 30 μg/ml, and a constant FA concentration of 10−5 m. A total of 180 different experimental conditions were tested. When cells were exposed to fotemustine prior to treatment with 5-FU, the final cytotoxic effects on both cell lines were additive or synergistic in the majority of cases (P<0.001). The 5-FU concentration was a determinant factor that modified the effects of the drug combination from antagonism (at low 5-FU concentrations) to synergism (high 5-FU concentrations;P<0.001). The addition of FA (10−5 m) resulted in a significant shift towards synergistic associations in both cell lines. Administration of 5-FU prior to treatment with fotemustine caused marked antagonism, which 10−5 m FA could not significantly shift towards simple additivity.
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Fischel, J.L., Formento, P., Berlion, M. et al. Sequence-dependent cytotoxic effects of the combination of a new nitrosourea, fotemustine, with 5-fluorouracil plus folinic acid. Cancer Chemother. Pharmacol. 28, 448–454 (1991). https://doi.org/10.1007/BF00685821
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DOI: https://doi.org/10.1007/BF00685821