Abstract
Purpose: Vinflunine (20′-20′-difluoro-3′,4′-dihydrovinorelbine), a novel derivative of vinorelbine characterized by marked antitumour activity in vivo in a series of experimental murine and human tumours is currently undergoing phase I evaluation. To investigate its potential for inclusion in combination chemotherapy regimens, this preclinical study was undertaken. The in vitro cytotoxicity of vinflunine incubated simultaneously with one of the following drugs was investigated: camptothecin, cisplatin, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, mitomycin C, paclitaxel or vinorelbine. Methods: The combinations were first evaluated in vitro against the A549 human non-small-cell lung cancer cell line using median-effect analyses. Results: The results revealed synergistic cytotoxicity when vinflunine was combined with cisplatin, mitomycin C, doxorubicin or 5-fluorouracil. Synergy was also observed when testing similar combinations against CCRF-CEM human leukaemia cells. Finally, these findings were comparable with those resulting from such combinations involving vinorelbine instead of vinflunine. Conclusion: Vinflunine appears a promising candidate for combining with other anticancer drugs.
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Received: 6 September 1999 / Accepted: 1 January 2000
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Barret, JM., Etiévant, C. & Hill, B. In vitro synergistic effects of vinflunine, a novel fluorinated vinca alkaloid, in combination with other anticancer drugs. Cancer Chemother Pharmacol 45, 471–476 (2000). https://doi.org/10.1007/s002800051021
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DOI: https://doi.org/10.1007/s002800051021