Anti-VEGF Cancer Chemotherapy and the Vasculature
Research type
Research Study
Full title
Endothelial Effects of VEGF Inhibition In Vivo in Man
IRAS ID
192297
Contact name
Ninian N Lang
Contact email
Sponsor organisation
NHS Greater Glasgow & Clyde
Duration of Study in the UK
1 years, 1 months, 3 days
Research summary
Developments in the treatment of cancer have improved survival from a large number of tumours, in part due to a group of chemotherapy drugs which block a protein called vascular endothelial growth factor (VEGF inhibitors (VEGFIs)). Whilst these drugs markedly improve cancer related prognosis, the majority of patients taking them develop high blood pressure and there is an increased risk of blood clots and heart failure.
Increased activity of endothelin, a substance which causes blood vessels to contract, is believed to be one of the main mechanisms contributing to the increased risk of cardiovascular complications associated with VEGFIs. Drugs which block the activity of endothelin (endothelin receptor antagonists) may therefore have a role in reducing the risk of VEGFI-associated hypertension. Before undertaking a clinical trial of endothelin receptor antagonists in patients taking VEGFIs we must first develop a better understanding of how endothelin contributes to the increased cardiovascular risk associated with VEGFIs.
We will address this question using a technique called forearm venous occlusion plethysmography. This is a robust, well-validated technique that is the gold standard method for assessing local vascular responses. It allows local vascular responses to agents to be assessed at doses 10 to 100 times lower than those that would affect the rest of the circulation.
We will administer the VEGFI bevacizumab at doses which should not affect the rest of the circulation. We will assess forearm vascular responses in terms of blood flow and the release of endothelin and blood clot dissolving factors. We will do this in the presence and absence of an endothelin receptor antagonist which will help to highlight or refute a role for endothelin receptor antagonists in treating VEGFI-associated hypertension. Data from this study will be used to inform the design of a clinical trial of endothelin receptor antagonists in patients taking VEGFIs.
REC name
West of Scotland REC 4
REC reference
16/WS/0031
Date of REC Opinion
9 Mar 2016
REC opinion
Further Information Favourable Opinion