TY - JOUR
T1 - Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity
AU - Shaked, Yuval
AU - Emmenegger, Urban
AU - Man, Shan
AU - Cervi, Dave
AU - Bertolini, Francesco
AU - Ben-David, Yaacov
AU - Kerbel, Robert S.
PY - 2005/11
Y1 - 2005/11
N2 - Low-dose metronomic chemotherapy is a promising therapeutic cancer treatment strategy thought to have an antiangiogenic basis. However, the advantages of reduced toxicity, increased efficacy in some cases, and ability to combine chemotherapy administered long term in this way with targeted therapies can be compromised by the empiricism associated with determining the optimum biologic dose (OBD). Using 4 distinct metronomic chemotherapy regimens in 4 different preclinical tumor models, including a hematologic malignancy, we established the OBD by determining the maximum efficacy associated with minimum or no toxicity. We then found each OBD to be strikingly correlated with the maximum reduction in viable peripheral blood circulating vascular endothelial growth factor receptor 2-positive (VEGFR-2+) endothelial precursors (CEPs). These results suggest that CEPs may serve as a pharmacodynamic biomarker to determine the OBD of metronomic chemotherapy regimens.
AB - Low-dose metronomic chemotherapy is a promising therapeutic cancer treatment strategy thought to have an antiangiogenic basis. However, the advantages of reduced toxicity, increased efficacy in some cases, and ability to combine chemotherapy administered long term in this way with targeted therapies can be compromised by the empiricism associated with determining the optimum biologic dose (OBD). Using 4 distinct metronomic chemotherapy regimens in 4 different preclinical tumor models, including a hematologic malignancy, we established the OBD by determining the maximum efficacy associated with minimum or no toxicity. We then found each OBD to be strikingly correlated with the maximum reduction in viable peripheral blood circulating vascular endothelial growth factor receptor 2-positive (VEGFR-2+) endothelial precursors (CEPs). These results suggest that CEPs may serve as a pharmacodynamic biomarker to determine the OBD of metronomic chemotherapy regimens.
UR - http://www.scopus.com/inward/record.url?scp=27644436870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27644436870&partnerID=8YFLogxK
U2 - 10.1182/blood-2005-04-1422
DO - 10.1182/blood-2005-04-1422
M3 - Article
C2 - 15998832
AN - SCOPUS:27644436870
VL - 106
SP - 3058
EP - 3061
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -