A randomized phase II study of metronomic cyclophosphamide and methotrexate (CM) with or without bevacizumab in patients with advanced breast cancer

Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy

“… 108 , 109 This approach has been shown to yield better survival than MTD in several preclinical tumor models and is currently being evaluated in multiple clinical trials ( Table S3 ). 108 , 109 , 110 , 111 , 112 , 113 Despite the initial belief that it works as an AAT, 114 , 115 it has been later shown to also affect the immune system as well as directly cancer cells, including the more chemoresistant stem-like cancer cells. The impact of metronomic chemotherapy on the tumor’s blood vessel formation might occur through the elevation of levels of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1).…”

“…Recently, Mayer et al. 113 demonstrated that the addition of bevacizumab in metronomic treatment with cyclophosphamide and methotrexate improved progression-free survival in patients with advanced breast cancer. Despite its pleiotropic effects, the metronomic regimen of cytotoxic drugs has not yet gained approval from the Food and Drug Administration (FDA).…”