Table 6 Comparison between vinflunine and vinorelbine regarding their preclinical effects and their clinical implications.

PRECLINICAL STUDIES:

IN VITRO

- mechanism of action^3,17

equal

- radiosensitising effect

equal

- cell cycle effect

equal

- cross-resistance to other MDR-inducing drugs⁴¹

VFL: least cross-resistant

- inducer of drug resistance^15,20

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 models^15,16

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

- tolerance^15,43,44

VFL: high level, superior to VRL

- anti-vascular effects^44,45

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:

- neurotoxicity^5,6,17,18,46

VFL: reduced relative to VRL

- therapeutic window^6,16,45,47

VFL: presumed to be wider than VRL