Annals of Oncology Advance Access published online on December 4, 2007
Annals of Oncology, doi:10.1093/annonc/mdm550
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© 2007 European Society for Medical Oncology
Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation
1 Avicenne Hospital Assistance Publique-Hôpitaux de Paris and Paris XIII University (EA3412), Bobigny
2 Lariboisière Hospital AP-HP and Institut National de la Santé et de la Recherche Médicale U689, Cardiovascular Research Center, Paris, France
* Correspondence to: Prof. B. I. Levy, Cardiovascular Research Center, Institut National de la Santé et de la Recherche Médicale U689, 41 Boulevard de la Chapelle, 75010 Paris, France. Tel: +33-1-42958087; Fax: +33-1-42813128; E-mail: levy{at}larib.inserm.fr
Arterial hypertension (HT) has been reported in all studies involving bevacizumab, an antiangiogenic agent designed to target vascular endothelial growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet clearly understood. As far as endothelial dysfunction and microvascular rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti-VEGF therapy could alter the microcirculation in nontumor tissues and, thus, result in an increase in blood pressure (BP).
We used intravital video microscopy to measure dermal capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser Doppler flowmetry combined with iontophoresis of pilocarpine (acetylcholine analogue). All measurements were carried out in 18 patients before and after a 6-month treatment with bevacizumab (mean cumulative dose: 3.16 ± 0.90 g).
Mean BP was increased after 6 months of therapy compared with baseline, from 129 ± 13/75 ± 7 mmHg to 145 ± 17/82 ± 7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared with the baseline, mean dermal capillary density at 6 months was significantly lower (75 ± 12 versus 83 ± 13/mm2; P < 0.0001), as well as pilocarpine-induced vasodilation (P < 0.05).
Thus, bevacizumab treatment resulted in endothelial dysfunction and capillary rarefaction; both changes are closely associated and could be responsible for the rise in BP observed in most patients.
angiogenesis, capillary rarefaction, endothelial function, hypertension, microcirculation
Received for publication June 30, 2007. Revision received October 13, 2007. Revision received November 2, 2007. Accepted for publication November 5, 2007.
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