Certain oral chemotherapy drugs can be used as antiangiogenic agents when administered at low doses at regular, frequent intervals. This type of treatment, called metronomic chemotherapy, offers the advantages of more convenient dosing and less debilitating side effects than conventional infusion chemotherapy. The oral chemotherapy drugs cyclophosphamide and methotrexate are often used together as metronomic therapy for breast cancer. In a clinical study that tested this combination in metastatic breast cancer patients, 21% experienced at least some tumor shrinkage.¹⁵

A second small study evaluated metronomic dosing of cyclophosphamide and capecitabine plus bevacizumab.¹⁶ In this study, 48% of patients experienced at least partial regression of their tumors. A large multinational phase 3 trial is underway to compare the effectiveness of one year of metronomic cyclophosphamide and methotrexate therapy versus observation following surgery and adjuvant chemotherapy in stage I-III ER-negative breast cancer.