BACKGROUND: Zoledronate has anti-bone resorption activity and is reported to reduce skeletal-related events. The objective of this study was to test the hypothesis that addition of zoledronate in chemotherapy is safe and effective in osteosarcoma.

MATERIAL AND METHODS: A total of 798 patients, age 25 years and above, with newly diagnosed high-grade surgically salvageable malignant osteosarcoma, were included in the trial. All patients had received standard chemotherapies (n=399). In addition, in a standard chemotherapy regimen, patients enrolled in the zoledronate group also received 10 courses of 4 mg intravenous infusions of zoledronate (n=399). Limb-sparing surgery was performed by orthopedic surgeons (n=798). Clinical assessment, laboratory monitoring, overall survival, event-free survival, and treatment-emergent adverse effects were evaluated. The chi-square independence-samples test was used for statistical analysis at 95% confidence level.

RESULTS: The histopathological response was the same for both groups (p=0.12). Addition of zoledronate to chemotherapy improved skeletal event-free survival (p=0.04) but decreased overall survival (p=0.02). Zoledronate induced hypocalcemia (p<0.0001), hypophosphatemia (p<0.0001), cardiotoxicity (p<0.0001), lung metastases (p=0.03), flu-like syndrome (p<0.0001), and ototoxicity (p=0.02), and elevated serum aspartate aminotransferase (p<0.0001) and serum alanine aminotransferase (p<0.0001).

CONCLUSIONS: The addition of zoledronate to standard chemotherapy in high-grade resectable osteosarcoma is detrimental and is not advised.

Keywords: Antineoplastic Combined Chemotherapy Protocols, Disease-Free Survival, Osteosarcoma, Survival Rate, Bone Neoplasms, Cisplatin, Combined Modality Therapy, Methotrexate, zoledronic acid