Adding the bisphosphonate zoledronate to chemotherapy and surgery did not improve event-free survival in patients with osteosarcoma, a study published in The Lancet Oncology has shown.1

Because preclinical data demonstrated an antitumor effect with zoledronate in osteosarcoma, researchers evaluated whether zoledronate combined with chemotherapy and surgery improved event-free survival in pediatric and adult patients with osteosarcoma.

For this multicenter, open-label, phase 3 trial, investigators enrolled 318 patients aged 5 to 50 years with newly diagnosed high-grade osteosarcoma from 40 centers in France.

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Adult patients older than 25 years were randomly assigned to receive doxorubicin, ifosfamide, and cisplatin with or without zoledronate 4 mg per infusion; patients aged less than 18 years received high-dose methotrexate-based chemotherapy with or without zoledronate 0.05 mg/kg per infusion; those aged 18 to 25 years were treated with either chemotherapy regimen at the discretion of the treating center, with or without zoledronate 0.05 mg/kg for the first 2 infusions, and 4 mg for the subsequent 8 infusions.

All patients received 10 infusions of zoledronate, 4 administered preoperatively and 6 given postoperatively.

At a median follow-up of 3.9 years, 3-year event-free survival was 63.4% (95% CI, 55.2-70.9) for patients who did not receive zoledronate, in contrast with 57.1% (95% CI, 48.8-65.0) for the zoledronate group (hazard ratio, 1.36; 95% CI, 0.95-1.96; P = .094). The study was stopped for futility.

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No major increase in any grade 3 or higher toxicity was observed with the addition of zoledronate, except for hypocalcemia and hypophosphatemia, both of which were expected. There was also no significant difference in orthopedic complications between the 2 groups.             


  1. Piperno-Neumann S, Le Deley MC, Redini F, Pacquement H, Marec-Bérard P, Petit P, et al. Zoledronate in combination with chemotherapy and surgery to treat osteosarcoma (OS2006): a randomised, multicentre, open-label, phase 3 trial [published online ahead of print June 17, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)30096-1.