23 February 2019 : Clinical Research
Addition of Zoledronate to Chemotherapy in Patients with Osteosarcoma Treated with Limb-Sparing Surgery: A Phase III Clinical TrialShenglong Li1EF*, Peng Chen2AC, Yi Pei1BD, Ke Zheng1AF, Wei Wang1ABD, Enduo Qiu1BCE, Xiaojing Zhang1ACE
Med Sci Monit 2019; 25:1429-1438
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, Neoplasm Metastasis, Osteosarcoma, Survival Analysis, Survival Rate, Adult, Aged, Bone Neoplasms, China, Cisplatin, Combined Modality Therapy, Doxorubicin, Methotrexate, Middle Aged, zoledronic acid
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