Anti-vascular effects of vinflunine in the MAC 15A transplantable adenocarcinoma model

Anti-vascular effects of the novel Vinca alkaloid, vinflunine have been inv estigated in the MAC 15A transplantable murine colon adenocarcinoma model a nd compared with those induced by the most recently identified clinically u seful third generation Vinca. Administration of the maximum tolerated dose of either vinflunine (50 mg kg(-1)) or vinorelbine (8 mg kg(-1)) resulted i n significant tumour growth delay with subsequent histological analysis rev ealing substantial haemorrhagic necrosis. This suggested possible anti-vasc ular effects and these were confirmed by Hoechst 33342 perfusion studies. V influnine, currently undergoing Phase I trials in Europe, was found to be a t least as effective as the clinically active vincristine and vinorelbine i n this model and, remarkably, produced anti-vascular effects at doses much lower than the maximum tolerated dose. Although vinflunine caused apoptosis in HUVEC monolayer cultures this event did not occur within the first 8 ho urs of exposure whereas vascular shutdown in vivo was observed within the f irst 4 hours. (C) 2001 Cancer Research Campaign.