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


CONCLUSIONS
Vinflunine appears a promising candidate for combining with other anticancer drugs.
Barret
J M
JM
Division de Cancérologie, Centre de Recherche Pierre Fabre, Castres, France.
Etiévant
C
C
Hill
B T
BT
D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004341:Drug Evaluation; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D008956:Models, Chemical; D017239:Paclitaxel / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077235:Vinorelbine; D000093542:Gemcitabine
D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D016685:Mitomycin; C111217:vinflunine; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine