Trial Information

A Study of the Pharmacodynamic Effects of Anti-Vascular Endothelial Growth

The well-established role of vascular endothelial growth factor (VEGF) in carcinogenesis and
tumor angiogenesis has led to the development of agents that target this pathway. Anti-VEGF
agents the VEGF monoclonal antibody bevacizumab, and the small molecule VEGF receptor
tyrosine kinase inhibitors. Angiogenic factors play a key role in the maintenance of lung
integrity and normal endothelial function. Endothelial dysfunction has been implicated in
hypertension, proteinuria and retinopathy. One of the major issues of anti-VEGF agents is
its long-term toxicity especially taking into account the lack of adequate knowledge in this
area and the possibility of prolonged periods of therapy in non-progressing patients.
Hypertension and proteinuria are commonly seen in patients treated with anti-VEGF agents. In
addition, we have also observed in a relatively high frequency of pulmonary air-filled
lesions in patients with malignancy in the lung treated with an anti-VEGF agent. Objectives
of this exploratory study are to 1) determine the effect of anti-vascular endothelial growth
factor (VEGF) on endothelial function 2) determine endothelial dysfunction as a marker of
early response and as an indicator for the development of hypertension and proteinuria 3)
characterize the effect of anti-VEGF therapy on the pulmonary function of patients with
malignancy (primary or secondary) involving the lung in patients treated with anti-VEGF
agents. Pharmacodynamic endpoints to be assessed are: blood pressure, brachial artery
reactivity, retinal microvessels, microalbuminuria and proteinuria, pulmonary function,
assess the effects of anti-VEGF therapy by assessing brachial artery reactivity, retinal
vasculature and pulmonary function in a subset of patients receiving anti-VEGF therapy. The
development of markers of endothelial dysfunction may result in the early identification of
patients who are non-responders or develop toxicity from anti-VEGF treatment.