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.


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.
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
N
N
Steeghs
T J
TJ
Rabelink
J
J
op 't Roodt
E
E
Batman
F H M
FH
Cluitmans
N I
NI
Weijl
E
E
de Koning
H
H
Gelderblom
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001794:Blood Pressure / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002196:Capillaries / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008046:Lip / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab