Annals of Oncology Advance Access published online on October 23, 2009
Annals of Oncology, doi:10.1093/annonc/mdp417
Reversibility of capillary density after discontinuation of bevacizumab treatment
1 Department of Clinical Oncology
2 Department of General Internal Medicine
3 Department of Nephrology, Leiden University Medical Center, Leiden
4 Department of Internal Medicine, Deaconess Hospital, Leiden
5 Department of Internal Medicine, Rijnland Hospital, Leiderdorp
6 Department of Internal Medicine, Bronovo Hospital, Den Haag, The Netherlands
* Correspondence to: Dr H. Gelderblom, Department of Clinical Oncology, Leiden University Medical Center, K1-P, PO Box 9600, 2300 RC Leiden, The Netherlands. Tel: +31-71-5263486; Fax: +31-71-5266760; E-mail: a.j.gelderblom{at}lumc.nl
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.
angiogenesis, bevacizumab, capillary density, hypertension, rarefaction, vascular endothelial growth factor inhibitor
Received for publication July 20, 2009. Accepted for publication July 22, 2009.