In vitro synergistic effects of vinflunine, a novel fluorinated vinca alkaloid, in combination with other anticancer drugs

Purpose: Vinflunine (20'-20'-difluoro-3',4'-dihydrovinorelbine), a novel de rivative of vinorelbine characterized by marked antitumour activity in vivo in a series of experimental murine and human tumours is currently undergoi ng phase I evaluation. To investigate its potential for inclusion in combin ation chemotherapy regimens, this preclinical study was undertaken. The in vitro cytotoxicity of vinflunine incubated simultaneously with one of the f ollowing drugs was investigated: camptothecin, cisplatin, doxorubicin, etop oside, 5-fluorouracil, gemcitabine, mitomycin C, paclitaxel or vinorelbine. Methods: The combinations were first evaluated in vitro against the A549 h uman non-small-cell lung cancer cell line using median-effect analyses. Res ults: The results revealed synergistic cytotoxicity when vinflunine was com bined with cisplatin, mitomycin C, doxorubicin or 5-fluorouracil. Synergy w as also observed when testing similar combinations against CCRF-CEM human l eukaemia cells. Finally, these findings were comparable with those resultin g from such combinations involving vinorelbine instead of vinflunine. Concl usion: Vinflunine appears a promising candidate for combining with other an ticancer drugs.