Low-dose oral metronomic chemotherapy prevents mobilization of endothelial progenitor cells into the blood of cancer patients.

UNLABELLED: Circulating endothelial progenitor cells (EPCs) actively supply cells that may participate in tumor angiogenesis. The differing effects of low-dose metronomic trofosfamide as opposed to conventional dose-dense chemotherapy on plasma levels of vascular endothelial growth factor (VEGF) and the numbers of circulating EPC are reported. PATIENTS AND METHODS: Blood samples were obtained from cancer patients, 18 receiving oral metronomic chemotherapy of trofosfamide with or without celecoxib, and 24 receiving conventional dose-dense chemotherapy, eight of them in adjuvant intention. Mononuclear cells were analyzed by flow cytometry for CD34, CD45 and vascular endothelial growth factor-receptor 2 (VEGF-R2) coexpression, defining EPCs, and for plasma levels of VEGF by ELISA at day 0, 10 and 21 of therapy.
RESULTS: After conventional dose-dense chemotherapy, the numbers of circulating EPCs and the VEGF plasma concentrations increased sharply, doubling pretherapeutic levels at day 21. In contrast, under low-dose metronomic chemotherapy, the numbers of circulating EPCs decreased significantly and VEGF plasma concentrations remained unchanged.
CONCLUSION: These observations provide evidence that conventional dose-dense chemotherapy leads to rebound EPC mobilization even when given with adjuvant intention, while low-dose metronomic scheduling of cytotoxic substances such as trofosfamide may sharply reduce EPC release into the circulation.