Abstract

The therapeutic concept of administering agents (cytotoxic/-static,non-cytotoxic and/or targeted drugs) continuously at lower doses - relative to MTDs in the case of cytostatic and cytotoxic drugs or continuously at tolerable doses as in the case of targeted drugs without drug-free breaks over extended periods - known as 'metronomic therapy' (MT), is increasingly being recognized as an experimental option for treating cancer. In comparison with MTD-defined chemotherapy (CHT) regimens, metronomic therapy has demonstrated reduced toxicity. More importantly, several phase II trials have shown that metronomic therapies showed anti-cancer activity in different cancer types with different drugs. The mechanistic basis of metronomic therapy using cytotoxic/static drugs is believed to be primarily anti-angiogenic, either by direct killing or inhibiting endothelial cells (ECs) in the tumor vasculature, killing bone-marrow-derived endothelial progenitor cells, stimulating the immune system, directly affecting tumor cells through a drug-driven effect as well as specificly inhibiting a target when targeting drugs were used in additional to metronomic therapy. The induction of senescence in cancer is another possible explanation for the principles behind 'metronomic therapy'.

Keywords:Metronomic therapy, anti-angiogenesis, cytotoxic drugs, cytostatic drugs, targeted drugs