Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for Management of Locally Advanced Breast Cancer With Serum VEGF as Primary Endpoint: The NEOZOL Study

In addition to its effects on bone metastases, zoledronic acid (ZA) has many other antitumor effects. The present randomized phase II trial studied the benefit of adding ZA to neoadjuvant chemotherapy for breast cancer with serum vascular endothelial growth factor (VEGF) as the primary endpoint. Neoadjuvant ZA showed a trend toward lowering serum VEGF levels. Further studies are needed with longer follow-up and additional relevant endpoints to confirm our results. Introduction: Neoadjuvant chemotherapy has become the treatment of choice for locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect. Antitumor effects of ZA, including the inhibition of cell adhesion to mineralized bone or the anti-angiogenic effect, have been demonstrated. However, the clinical significance of these effects remains to be determined. Materials and Methods: We undertook a multicenter open-label randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the evolution of serum VEGF. Results: The data from 24 patients were included in the ZA group and 26 in the control group. The evolution of serum VEGF was slightly in favor of ZA at 5.5 months (0.7% vs. 7.5%), without reaching statistical significance (P = .52). The secondary endpoints were the breast conservation rate (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95% confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal failure were observed in either group. Conclusion: ZA is an antitumor drug of interest because of its multiple effects on tumor biology. Larger trials with longer follow-up that include additional endpoints such as relapse and survival rates would be of interest. (C) 2018 Elsevier Inc. All rights reserved.