Purpose: On the basis of stimulating data on animals reporting that weekly regimens ofzoledronic acid (ZA) were effective in reducing skeletal tumor burden, we designed a study onhumans to investigate the potential antiangiogenic role of a weekly low-dose therapy with ZA inpatients with malignancies.Experimental Design: Twenty-six consecutive patients with advanced solid cancer and bonemetastases received1mg of ZA every week for four times (days1,7,14, and 21) followed by 4 mgof ZA with a standard 28-day schedule repeated thrice (days 28, 56, and 84). Patients wereprospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) justbefore the beginning of drug infusion (0) and again at 7,14, 21, 28, 56, and 84 days after the firstZA infusion.Results: The median VEGF basal value showed an early statistically significant (P = 0.038)decrease 7 days after the first1-mg infusion of ZA.This effect onVEGF-circulating levels persistedalso after the following 1-mg infusions at 14 (P = 0.002), 21 (P = 0.001), and 28 days(P = 0.008). Interestingly, the decrease of VEGF-circulating levels persisted also at eachprogrammed time point during the second phase of the study (ZA 4 mg every 4 weeks). Nosignificant differences were recorded in platelet levels,WBC count, or hemoglobin concentrationbefore and after each ZA infusion.Conclusions: In the present study,we report that a repeated low-dose therapywith ZA is able toinduce an early significant and long-lasting decrease ofVEGF levels in cancer patients.

Repeated intermittent low-dose therapy with zoledronic Acid induces an early, sustained, and long-lasting decrease of peripheral vascular endothelial growth factor levels in cancer patients

SANTINI D;VINCENZI B;BATTISTONI F;ROCCI L;ANGELETTI S;DICUONZO G;TONINI G
2007-01-01

Abstract

Purpose: On the basis of stimulating data on animals reporting that weekly regimens ofzoledronic acid (ZA) were effective in reducing skeletal tumor burden, we designed a study onhumans to investigate the potential antiangiogenic role of a weekly low-dose therapy with ZA inpatients with malignancies.Experimental Design: Twenty-six consecutive patients with advanced solid cancer and bonemetastases received1mg of ZA every week for four times (days1,7,14, and 21) followed by 4 mgof ZA with a standard 28-day schedule repeated thrice (days 28, 56, and 84). Patients wereprospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) justbefore the beginning of drug infusion (0) and again at 7,14, 21, 28, 56, and 84 days after the firstZA infusion.Results: The median VEGF basal value showed an early statistically significant (P = 0.038)decrease 7 days after the first1-mg infusion of ZA.This effect onVEGF-circulating levels persistedalso after the following 1-mg infusions at 14 (P = 0.002), 21 (P = 0.001), and 28 days(P = 0.008). Interestingly, the decrease of VEGF-circulating levels persisted also at eachprogrammed time point during the second phase of the study (ZA 4 mg every 4 weeks). Nosignificant differences were recorded in platelet levels,WBC count, or hemoglobin concentrationbefore and after each ZA infusion.Conclusions: In the present study,we report that a repeated low-dose therapywith ZA is able toinduce an early significant and long-lasting decrease ofVEGF levels in cancer patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/7721
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