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  • Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: A report from the Children's Oncology Group EUROPEAN JOURNAL OF CANCER Goldsby, R. E., Fan, T. M., Villaluna, D., Wagner, L. M., Isakoff, M. S., Meyer, J., Randall, R. L., Lee, S., Kim, G., Bernstein, M., Gorlick, R., Krailo, M., Marina, N. 2013; 49 (10): 2384-2391


    Patients with metastatic osteosarcoma (OS) have a poor outcome with conventional therapies. Zoledronic acid (ZA) is a third-generation bisphosphonate that reduces skeletal-related events in many adult cancers, and pre-clinical data suggest a possible benefit in OS. This study assessed the maximum tolerated dose (MTD) and the feasibility of ZA when combined with chemotherapy in patients with metastatic OS.Patients with a histological diagnosis of OS were eligible if they were <40years of age, had initially metastatic disease and met organ function requirements. Treatment combined surgery and a conventional chemotherapy regimen. ZA was given concurrent with chemotherapy for a total of eight doses over 36weeks. Three dose levels of ZA were tested: 1.2mg/m(2) [max 2mg], 2.3mg/m(2) [max 4mg] and 3.5mg/m(2) [max 6mg]. The MTD was determined during induction. Six patients were to be treated at each dose level, with an additional six patients treated with the MTD to help assess post-induction feasibility.Twenty-four patients (median age 13.5years [range, 7-22]; 16 females) were treated. Five patients experienced dose-limiting toxicities (DLTs) during induction, including three patients treated with 3.5mg/m(2). DLTs included hypophosphatemia, hypokalemia, hyponatremia, mucositis, limb pain and limb oedema. There were no reports of excessive renal toxicity or osteonecrosis of the jaw. The MTD was defined as 2.3mg/m(2) (max 4mg).ZA can be safely combined with conventional chemotherapy with an MTD of 2.3mg/m(2) (max 4mg) for patients with metastatic osteosarcoma.

    View details for DOI 10.1016/j.ejca.2013.03.018

    View details for Web of Science ID 000320504200012

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