title: Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial.
abstract: BACKGROUND
  Giant cell tumor of bone (GCTB) is a rare primary bone tumor, characterized by osteoclast-like giant cells that express receptor activator of nuclear factor-kappa B (RANK), and stromal cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. A RANKL-specific inhibitor, denosumab, was predicted to reduce osteolysis and control disease progression in patients with GCTB.
  
  
  METHODS
  Seventeen patients with GCTB were enrolled. Patients were treated with denosumab at 120 mg every 4 weeks, with a loading dose of 120 mg on days 8 and 15. To evaluate efficacy, objective tumor response was evaluated prospectively by an independent imaging facility on the basis of prespecified criteria.
  
  
  RESULTS
  The proportion of patients with an objective tumor response was 88% based on best response using any tumor response criteria. The proportion of patients with an objective tumor response using individual response criteria was 35% based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, 82% based on the modified European Organization for Research and Treatment of Cancer (EORTC) criteria, and 71% based on inverse Choi criteria. The median time of study treatment was 13.1 months.
  
  
  CONCLUSIONS
  The findings demonstrate that denosumab has robust clinical efficacy in the treatment of GCTB.
authors.affiliation: Department of Orthopaedic Surgery, Osaka National Hospital, Osaka uedat@onh.go.jp.
authors.forename: T
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo.
authors.forename: H
authors.initials: H
authors.lastname: Morioka
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya.
authors.forename: Y
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Orthopaedic Surgery, Osaka National Hospital, Osaka.
authors.forename: S
authors.initials: S
authors.lastname: Kakunaga
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa.
authors.forename: H
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Daiichi Sankyo Co., Ltd, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Asami
authors.affiliation: Daiichi Sankyo Co., Ltd, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: T
authors.initials: T
authors.lastname: Yoneda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069448:Denosumab / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D000069448:Denosumab
keywords: RANKL; denosumab; giant cell tumor of bone; objective tumor response; primary bone tumor