Metronomic chemotherapy

1. The negative effects of metronomic chemotherapy are substantially less severe than those of conventional chemotherapy. Its significantly better toxicity profile allows for extended dosing.

2. The metronomic chemotherapy is much easier to administer.

3. Metronomic chemotherapy Helps to prevent local and distant metastases.

4. Metronomic chemotherapy has a significantly stronger antiangiogenic impact

• while conventional therapy focuses on tumor cells that are actively multiplying, metronomic chemotherapy targets endothelial cells in the expanding tumor vasculature.
• tumor endothelial cells are a significant target for metronomic chemotherapeutic activity.
• metronomic chemotherapy prevents the growth of endothelial progenitor cells, which are crucial for the development of tumor vessels ¹. Conversely, chemotherapy at maximal permissible doses stimulates endothelial progenitor cells ².
• metronomic chemotherapy also induces antiangiogenic thrombospondin-1 protein ³.
• metronomic chemotherapy blocks HIF-1-alpha, the hypoxia-inducible factor that sets off a series of signaling events that lead to tumor angiogenesis, glycolysis, and other mechanisms that promote cancer progression and metastasis ⁴.
• metronomic chemotherapy decreases the circulating levels of vascular endothelial growth factor VEGF ⁵.

5. It improves the antitumoral response

• it lowers Treg cells, which, by limiting the immune response, contribute to tumor immunotolerance ⁶, and it improves the immune NK-cell and T-cell response via this Treg inhibitory action ⁷.
• it enhances the cytotoxic response of dendritic cells by amplifying tumor antigen presentation ⁸ and thus increases the immunogenic response to tumor cell death ⁹.
• it reduces the number of tumor stem cells ¹⁰.