Reversibility of capillary density after discontinuation of bevacizumab treatment

Steeghs, N.; Rabelink, T.J.; Roodt, J.O. 't; Batman, E.; Cluitmans, F.H.M.; Weijl, N.I.; ... ; Gelderblom, H. (2010)

Article / Letter to editor

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.

• All authors: Steeghs, N.; Rabelink, T.J.; Roodt, J.O. 't; Batman, E.; Cluitmans, F.H.M.; Weijl, N.I.; Koning, E. de; Gelderblom, H.
• Date: 2010-05-31
• Volume: 21
• Issue: 5
• Pages: 1100 - 5
• DOI: doi:10.1093/annonc/mdp417