Zoledronic Phosphonic Acid (zometa) With Bone Metastases Of Breast Cancer Patients Vegf Levels In Peripheral Blood Research

Objective:Zoledronic acid(ZOL) has direct and indirect antitumor effects,however, the pharmacokinetics of the drug in breast cancer patients remains to be elucidated and optimized.The main study objectives were to compare the effects of ZOL on bone resorption,angiogenesis,tumor markers and time to disease progression between a weekly low dose versus a conventional dosage.Methods:Sixty breast cancer patients with bone metastases were recruited to a randomized phaseâ…¡trial.They were randomized to either ZOL 1 mgâ…£weekly for 4 doses or a single dose of ZOL 4 mgâ…£.No other antitumor treatments were administered during the first month after randomization.Serial blood samples were collected on day 1,15 and 29 to measure markers for bone resorption(N-telopeptide), angiogenesis(VEGF) and tumor burden(CEA and CA15-3).Results:Compared to a single-dose administration,weekly low-dose of ZOL resulted within the first 4 weeks in significantly greater reductions in serum levels of VEGF and N-telopeptide,with more reduction towards the end of the first month of treatment. Patients who received metronomic ZOL had a substantially longer median TTP(7.0 months,95%CI,6.1-7.9 months) than those who had a single dose of ZOL(2.8 months,95%CI,0-5.7 months;P=0.076).Conclusion:Metronomic use of low-dose ZOL appeared to be more effective than conventional regimen in reduction of circulating VEGF and N-telopeptide,and in prolonging TTP.This dosing schedule should be further assessed in phaseâ…¢trials. (ClinicalTrials.gov number,NCT00524849)...