Table 2. Criteria for an antiangiogenic approach ofmetronomic CHT.

• Strong differential cytotoxicity between cancer cells and endothelial cells
• altered function of endothelial cells shown in dynamic contrast enhanced magnetic resonance imaging (DCEMRI) or contrast enhanced ultrasonic examinations (CEUS) by changes in the permeability and blood-flow in tumors
• changes of mechanistic effects (e.g. biomarker changes: IL-1 &6, uPA, VEGF, VEGFR1&2, bFGF, Ang 1&2, MMP- 2&9, vessel density etc.)
• inhibition of angiogenesis in vivo & in vitro (in vivo models at best only with spontaneous, slow growing tumors)