Denosumab and giant cell tumour of bone-a review and future management considerations.

Giant cell tumour of bone (gctb) is one type of giant-cell-rich bone lesion characterized by the presence of numerous multinucleated osteoclast-type giant cells. Giant cells are known to express rankl (receptor activator of nuclear factor κB ligand) and are responsible for the aggressive osteolytic nature of the tumour. No available treatment option is definitively effective in curing this disease, especially in surgically unsalvageable cases. In recent years, several studies of denosumab in patients with advanced or unresectable gctb have shown objective changes in tumour composition, reduced bony destruction, and clinical benefit. Denosumab is a fully human monoclonal antibody that targets and binds with high affinity and specificity to rankl. Several large phase iii studies have shown that denosumab is more effective than bisphosphonates in reducing skeletal morbidity arising from a wide range of tumours and that it can delay bone metastasis. The relevant articles are reviewed here. The controversies related to the future use of denosumab in the treatment of gctb are discussed.

[1]  M. Suarez‐Almazor,et al.  Denosumab in patients with cancer and skeletal metastases: a systematic review and meta-analysis. , 2013, Cancer treatment reviews.

[2]  F. Sutcliffe,et al.  NICE guidance on denosumab for prevention of skeletal-related events in adults with bone metastases from solid tumours. , 2012, The Lancet. Oncology.

[3]  E. McCloskey,et al.  Bisphosphonates in oncology. , 2011, Bone.

[4]  F. Sim,et al.  Recurrent Giant Cell Tumor of Long Bones: Analysis of Surgical Management , 2011, Clinical orthopaedics and related research.

[5]  G. Scagliotti,et al.  Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  M. Carducci,et al.  Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study , 2011, The Lancet.

[7]  F. Sim,et al.  Giant Cell Tumor of Bone: Risk Factors for Recurrence , 2011, Clinical orthopaedics and related research.

[8]  Y. Fujiwara,et al.  Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  P. Rutkowski,et al.  The megavoltage radiation therapy in treatment of patients with advanced or difficult giant cell tumors of bone. , 2010, International journal of radiation oncology, biology, physics.

[10]  David M. Thomas,et al.  Safety of denosumab in giant-cell tumour of bone. , 2010, The Lancet. Oncology.

[11]  A. Kyrgidis,et al.  Safety and efficacy of denosumab in giant-cell tumour of bone. , 2010, The Lancet. Oncology.

[12]  P. Choong,et al.  RANK-Fc inhibits malignancy via inhibiting ERK activation and evoking caspase-3-mediated anoikis in human osteosarcoma cells , 2010, Clinical & Experimental Metastasis.

[13]  Sakae Tanaka,et al.  Systemic RANK‐Fc protein therapy is efficacious against primary osteosarcoma growth in a murine model via activity against osteoclasts , 2010, The Journal of pharmacy and pharmacology.

[14]  David M. Thomas,et al.  Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. , 2010, The Lancet. Oncology.

[15]  M. Balke,et al.  Denosumab: a breakthrough in treatment of giant-cell tumour of bone? , 2010, The Lancet. Oncology.

[16]  K. Schwartz,et al.  The epidemiology of malignant giant cell tumors of bone: an analysis of data from the Surveillance, Epidemiology and End Results Program (1975–2004) , 2009, Rare tumors.

[17]  F. Saad,et al.  Denosumab in men receiving androgen-deprivation therapy for prostate cancer. , 2009, The New England journal of medicine.

[18]  X. Mariette,et al.  Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  R. Chlebowski,et al.  Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  P. Gascón,et al.  Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  C. Goswami,et al.  Post-irradiation angiosarcoma of bone. , 2007, Journal of cancer research and therapeutics.

[22]  W. Dougall,et al.  The RANK/RANKL/OPG triad in cancer-induced bone diseases , 2007, Cancer and Metastasis Reviews.

[23]  J. Body,et al.  A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. , 2006, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  S. Cross,et al.  Osteoprotegerin (OPG) Expression by Breast Cancer Cells in vitro and Breast Tumours in vivo – A Role in Tumour Cell Survival? , 2005, Breast Cancer Research and Treatment.

[25]  Colin R Dunstan,et al.  A Single‐Dose Placebo‐Controlled Study of AMG 162, a Fully Human Monoclonal Antibody to RANKL, in Postmenopausal Women , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[26]  G. Roodman Mechanisms of bone metastasis. , 2004, Discovery medicine.

[27]  Steven W. Martin,et al.  A Phase I study of AMGN‐0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases , 2003, Cancer.

[28]  R. Kitazawa,et al.  RANK ligand is a prerequisite for cancer‐associated osteolytic lesions , 2002, The Journal of pathology.

[29]  L. Kaban,et al.  Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. , 2002, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[30]  G. Mundy Metastasis: Metastasis to bone: causes, consequences and therapeutic opportunities , 2002, Nature Reviews Cancer.

[31]  A. Yasko Interferon therapy for vascular tumors of bone , 2001 .

[32]  M. Zheng,et al.  Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kappaB in giant cell tumor of bone: possible involvement in tumor cell-induced osteoclast-like cell formation. , 2000 .

[33]  L. White,et al.  Treatment of giant-cell tumors of long bones with curettage and bone-grafting. , 1999, The Journal of bone and joint surgery. American volume.

[34]  G. Matcuk,et al.  Giant cell tumor of bone: review, mimics, and new developments in treatment. , 2013, Radiographics : a review publication of the Radiological Society of North America, Inc.

[35]  J. Blay,et al.  An unusual giant cell tumor of the thyroid: case report and review of the literature. , 2013, The Journal of clinical endocrinology and metabolism.

[36]  P. Royle,et al.  Denosumab for treatment of bone metastases secondary to solid tumours: systematic review and network meta-analysis. , 2013, European journal of cancer.

[37]  L. Carmona,et al.  Denosumab for the treatment of osteoporosis: a systematic literature review. , 2013, Reumatologia clinica.

[38]  L. Tse,et al.  Bisphosphonates reduce local recurrence in extremity giant cell tumor of bone: a case-control study. , 2008, Bone.

[39]  M. Szendrői Giant-cell tumour of bone. , 2004, The Journal of bone and joint surgery. British volume.

[40]  K. Siebenrock,et al.  Giant-cell tumour of bone metastasising to the lungs: A long-term follow-up , 1998 .

[41]  R. Capanna,et al.  Curettage of giant cell tumor of bone. Introduction--material and methods. , 1990, La Chirurgia degli organi di movimento.

[42]  N. Baldini,et al.  Giant-cell tumor of bone. , 1987, The Journal of bone and joint surgery. American volume.