Jm. Barret et al., In vitro synergistic effects of vinflunine, a novel fluorinated vinca alkaloid, in combination with other anticancer drugs, CANC CHEMOT, 45(6), 2000, pp. 471-476
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.