Table 6.

Comparison between vinflunine and vinorelbine regarding their preclinical effects and their clinical implications.

PRECLINICAL STUDIES:
IN VITRO	VFL vs VRL
- mechanism of action3,17	equal
- radiosensitising effect	equal
- cell cycle effect	equal
- cross-resistance to other MDR-inducing drugs41	VFL: least cross-resistant
- inducer of drug resistance15,20	VFL far less potent than VRL at 2 × IC50: resistance after 8 months instead of within 2 weeks for VRL
- combination with other chemotherapeutic agents42	VFL: high level of synergy
IN VIVO
- efficacy against a series of murine and human tumour experimental models15,16	VFL definite superiority to VRL
	VFL: high or moderate activity in 64% (7 of 11)
	VRL: moderate activity in 27% (3 of 11)
- inducer of drug resistance20	VFL far less readily than VRL
	10 mg/kg vs 2.5 mg/kg – P388: complete resistance after 22 weeks instead of after 5 weeks
- tolerance15,43,44	VFL: high level, superior to VRL
- anti-vascular effects44,45	VFL: at doses much lower (5-fold) than the MTD
- anti-angiogenic effects45	VFL: at doses below the optimum effective single dose (40-20-fold lower than its MTD)
- activity against metastases45	VFL: significant effects at low doses (16-fold lower than the MTD)
CLINICAL IMPLICATIONS:
- neurotoxicity5,6,17,18,46	VFL: reduced relative to VRL
- therapeutic window6,16,45,47	VFL: presumed to be wider than VRL