Zoledronic Acid To Prevent Bone Metastasis In Patients With Stage ⅢB Or Stage Ⅳ Lung Cancer: Results Of Multicenter,Open-lable,Randomized Controlled Study

Background:Advanced lung cancer exhibits a strong predilection to develop to bone metastases,which would bring not only skeletal-related events(SREs),including pain,pathologic fractures,hypercalcemia,spinal cord compression,bone marrow infiltration,but also the mental affliction to the patients,which greatly increase health care costs and reduce the quality of life and overall survial(OS)of the patients.Therefore,it is not surprising therefore that Preventing or delaying bone metastases may improve outcomes.Objective:This study was designed to evaluate the preventive role and safety of zoledronic acid(ZOL)on bone metastasis in patients with stage IIIB or stage IV lung cancer but without bone metastases.Methods:Eligible patients during March 2013 to March 2015 were randomized to receive first-line therapy with(treatment group)or without(control group)ZO L 4mg as a 15-min infusion every 3 months for 4 cycles.At development of bone metastases,all patients were to receive ZO L 4mg every 3-4 weeks according to the guidelines.The primary endpoint were the incidence and bone metastases occurrence time;the secondary endpoints were progression-free survival(PFS),OS and adverse reactions.Results:No significant intergroup differences were observed in time to occurrence of bone metastases and rate of bone metastases,PFS,or OS(P > 0.05).3 patients in the experimental arm(62)and 3 patients in the control arm(71)developed bone metastases at 6 months;9 patients in the experimental arm and 11 patients in the control arm developed bone metastases at 12 months.The median time to occurrence of bone metastases was 7.7 months with ZOL versus 7.9 months for control.Median PFS was 8.2 months with ZOL versus 9.0 months for control.Median OS was 11.5 months with ZOL versus 13.0 months for control.There was no statistically significant between the treatment-related adverse reactions of two groups(P>0.05),but with the exception of hypocalcemia(2 vs 0).Conclusion:This research did not demonstrate that ZOL could prevent bone metastasis occurrence in stage IIIB or stage IV patients with lung cancer,but ZOL were well tolerated and safe in clinical treatment.Low cycles of therapy with ZO L and the low rates of bone metastases possibly limit the potential ZOL impact on disease course.