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This combination therapy consists of the bisphosphonate zoledronic acid (Zometa) administered in conjunction with a standard neoadjuvant chemotherapy regimen comprising doxorubicin and cyclophosphamide followed by docetaxel. Developed and evaluated by Hospices Civils de Lyon in the Phase 2 NEOZOL trial, this regimen was investigated for the treatment of locally advanced, HER2-negative breast cancer. Zoledronic acid, originally indicated for bone metastases and osteoporosis, was hypothesized to enhance the efficacy of neoadjuvant chemotherapy through multiple mechanisms, including direct anti-tumor activity (induction of apoptosis and inhibition of tumor cell growth), anti-angiogenic effects (reduction of serum VEGF levels), and the prevention of early bone micrometastases. While the trial explored breast conservation rates and various biological markers, the addition of zoledronic acid did not reach statistical significance for its primary endpoint of serum VEGF evolution.
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