Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, in vitro

Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.Vinflunine and vinorelbine induced a comparable radiosensitising effect (p-value never below 0.01) when cells were incubated for 24 h immediately prior to radiation. Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines. Similar results, with small cell line-related differences, were observed with vinflunine.The radiosensitising effects of both semisynthetic vinca alkaloids were comparable (not statistically different) and nearly always cell line-specific and concentration-dependent. The cell cycle effects could be related to the observed radiosensitising effects. Considering the more favourable toxicity profile of vinflunine, this agent might be more promising than vinorelbine for chemoradiation studies in the clinic.Vinca alkaloids are an important class of antitumour agents used in chemotherapy, either as single agents or in combination regimens. Semisynthetic vinca alkaloids, such as vinorelbine (VRL) and most recently vinflunine (VFL), have been developed to improve the therapeutic index [1]. Like the other vinca alkaloids, VRL and VFL exert their antitumour effect by binding to tubulin, the major component of microtubules in mitotic spindles. They diminish microtubule dynamics and assembly, which ultimately results in cell cycle arrest at the metaphase/anaphase transition [2,3]. However, they also differ from the naturally occurring vinca alkaloids in chemical structure, microtubule selectivity, and toxicity. In that respect, the capacity of VRL to bind preferentially to mitotic rather than axonal microtubules may imply that occurrence of neurotoxicity is less likely with VRL than with vinblastine or vincristine, and may predict a wider therapeutic window for VRL [4]. VFL also displays some differences in