Reversibility of capillary density after discontinuation of bevacizumab treatment

Background: Vascular endothelial growth factor (VEGF) inhibition is known to decrease capillary density. Decreased capillary density may be the basis for VEGF inhibitor-related side-effects. We investigated whether the effects of bevacizumab on capillary density are reversible. Patients and methods: Capillary density, assessed by sidestream dark field imaging of the mucosal surface of the lip, was measured at baseline, after 6 weeks of bevacizumab treatment and >3 months after discontinuation. Additional measurements included blood pressure (BP) measurements, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD) and aortic pulse wave velocity (PWV). Results: Fourteen patients were included. Seven patients completed measurements at all three predefined time points. Capillary density significantly decreased after 6 weeks of bevacizumab treatment and was reversible after discontinuation of bevacizumab (P = 0.00001 using a general linear model repeated measures test). BP, FMD and NMD remained unchanged. Mean PWV increased after 6 weeks of treatment (P = 0.027) and decreased after bevacizumab discontinuation. Among the six patients with the best response were the three patients showing the clearest decrease in capillary density after 6 weeks of bevacizumab treatment. Conclusions: Bevacizumab-induced decrease in capillary density is reversible. Noninvasive assessment of capillary density during treatment with antiangiogenic drugs may be useful as a marker of treatment efficacy.