VASCular Impact of Angiogenic Treatment in Patients With Advanced Colorectal Cancer
Status:
Recruiting
Trial end date:
2022-11-05
Target enrollment:
Participant gender:
Summary
Antiangiogenic treatments are used in many tumor locations such as metastatic colorectal
cancer (mCRC) with a significant improvement in carcinological results on overall survival
and / or progression-free survival. However, their use is characterized by an increase in
side effects and in particular cardiovascular effects such as high blood pressure
(hypertension). One of the main classes of antiangiogens used in this indication is that of
monoclonal antibodies, the leader of which is bevacizumab (Avastin®, Roche, Bale,
Switzerland). Bevacizumab works by inhibiting endothelial vascular growth factor-dependent
neoangiogenesis (vascular endothelial growth factor VEGF). In the reference studies, the
inhibition of VEGF, whether extracellular (monoclonal antibody directed against VEGFA) or
intracellular (receptor inhibitors with tyrosine kinase activity), induces hypertension of
all grades, observed in 25% to 40 % of patients including 8 to 17% of severe grades (≥ grade
3 NCI-CTCAE). In terms of pathophysiology, inhibition of VEGFA results in a decrease in the
availability of nitric oxide (NO) at the endothelial level and the appearance of arteriolar
rarefaction. This induces an increase in peripheral resistance responsible ultimately for an
increase in blood pressure. The occurrence of hypertension induced by anti-VEGF treatment
seems to be predictive of the carcinological response in certain oncological situations such
as metastatic breast cancer9, glioblastoma and mRCC. Furthermore, it has also been shown that
there is an early attack on the elastic conductance arteries (branches of the aorta and its
main ones) characterized by an increase in their rigidity in patients exposed to a VEGF
receptor inhibitor with tyrosine activity. kinase or bevacizumab. This increase, whose poor
prognostic impact is known at the cardiovascular level is largely independent of the rise in
blood pressure and reflects a direct toxicity of treatments at the level of the artery wall.
This increase in rigidity, refused when the pressure rises, would be predictive of a low
carcinological response rate at 6 months. However, these data are based on populations that
are heterogeneous in terms of carcinology and the position prior to or concomitant with other
antineoplastic treatments.
In this context, the evaluation of arterial stiffness in the same patient population would
make it possible to better define the involvement of the conductive arteries in a clearly
defined clinical situation. Joint measurements of the plasma concentration of the treatment
as well as those of factors derived from the endothelium and circulating tumor markers which,
to our knowledge, have never been carried out in these patients, would make it possible to
better specify the mechanisms of involvement and the links between exposure, arterial
toxicity and carcinologic efficacy of bevacizumab. Of course, in order to assess more
precisely the inherent impact of chemotherapy on the conductance arteries, the evolution of
arterial stiffness must take into account the possible effects in patients receiving, for
essentially clinical and biological reasons, systemic treatment without antiangiogenic.