223-Radium for metastatic osteosarcoma: combination therapy with other agents and external beam radiotherapy

Background Bone-seeking radiopharmaceuticals can deposit radiation selectively to some osteosarcoma tumours because of the bone-forming nature of this cancer. Objectives This is the first report of using 223-radium, an alpha-emitting calcium analogue with a high therapeutic index, in combination therapy with other agents in 15 patients with metastatic osteoblastic osteosarcoma. Methods Candidates for alpha-radiotherapy if Tc-99m-MDP bone scan had avid bone-forming lesions and no therapy of higher priority (eg, definitive surgery). Monthly 223-radium infusions (1.49 mu Ci/kg or 55.13 kBq/kg) were given. Results The median infusion number was three and the average time to progression was 4.3 months for this cohort receiving 223-radium+other agents. Agents provided during 223-radium included (1) drugs to reduce skeletal complications: monthly denosumab (n=13) or zolendronate (n=1); (2) agents with antivascular endothelial growth factor activity, pazopanib (n=8) or sorafenib (n=1), (3) alkylating agents: oral cyclophosphamide (n=1) or ifosfamide, given as a 14-day continuous infusion (n=1, two cycles), (4) high-dose methotrexate (n=1), pegylated liposomal doxorubicin (n=1); and (5) two other combinations: nivolumab and everolimus (n=1) and rapamycin and auranofin (n=1). Radiation therapy, including stereotactic body radiotherapy (SBRT), was also given to 11 patients concurrently with 223-radium (n=2), after 223-radium completion (n=3), or both concurrently and then sequentially for other sites (n=6). After 223-radium infusions, patients without RT had a median overall survival of 4.3 months compared with those with SBRT and/or RT, who had a median overall survival of 13.5 months. Conclusion Although only 1/15 of patients with osteoblastic osteosarcoma still remain alive after 223-radium, overall survival