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Blood. 2006 Jul 15;108(2):452-9. Epub 2006 Mar 16.
endothelial-cell kinetics and viability predict survival in breast
cancer patients receiving metronomic chemotherapy.
Mancuso P, Colleoni M, Calleri A, Orlando L, Maisonneuve P, Pruneri G, Agliano A, Goldhirsch A, Shaked Y, Kerbel RS, Bertolini F.
Division of Hematology-Oncology, Department of Medicine, European Institute of Oncology, Milan, Italy.
agents and therapeutic strategies have entered the clinical oncology
arena. The classical tumor size measurements defined to monitor
efficacy of chemotherapy, however, might not be appropriate for these
newer therapeutics. We previously found that circulating endothelial
cells (CECs) were increased in number and more viable in cancer
patients compared with control subjects. We investigated the
correlation between CEC kinetics and clinical outcome in patients with
advanced breast cancer receiving metronomic chemotherapy, a therapeutic
strategy associated with antiangiogenic activity and anticancer
CEC number and viability were measured by flow cytometry in
patients and in preclinical models. CECs were decreased in patients for
whom no overall clinical benefit (defined as a clinical response or a
stable disease) was observed compared with those who had a clinical
benefit (P = .015). This difference was due to an increased fraction of
apoptotic CECs in patients with a clinical benefit. Univariate and
multivariate analyses indicated that CEC values greater than 11/microL
were associated with a longer progression-free survival (P = .001) and
an improved overall survival (P = .005). Preclinical models indicated
that the source of apoptotic CECs was most likely the tumor
vasculature. CEC kinetics and viability are very promising as
predictors of clinical response in patients undergoing metronomic