Oncology
Short Communication
RANK Ligand Blockade with Denosumab in Combination with Sorafenib in Chemorefractory Osteosarcoma: A Possible Step Forward?Cathomas R.a · Rothermundt C.b · Bode B.c · Fuchs B.d · von Moos R.a · Schwitter M.aaDivision of Oncology/Haematology, Kantonsspital Graubünden, Chur, bDivision of Oncology/Haematology, Kantonsspital St. Gallen, St. Gallen, and cInstitute of Surgical Pathology, University Hospital Zurich, and dSarcoma Center and Laboratory for Orthopaedic Research, Department of Orthopaedics, Balgrist University Hospital Zurich, Zurich, Switzerland
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Article / Publication Details
Received: August 31, 2014
Accepted: November 12, 2014
Published online: December 17, 2014
Issue release date: March 2015
Number of Print Pages: 4
Number of Figures: 2
Number of Tables: 0
ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)
For additional information: https://www.karger.com/OCL
Abstract
Background: There is no established systemic treatment option for unresectable osteosarcoma progressing after standard chemotherapy. A recently published clinical trial has demonstrated some activity of sorafenib in this situation. Preclinical research suggests a role for the inhibition of the receptor activator of nuclear factor-ĸB ligand (RANKL), but no clinical data have been reported so far. Case Report: A 37-year-old man was diagnosed with unresectable osteoblastic, osteoblastoma-like osteosarcoma in the C7/Th1 vertebra. The tumour progressed locally despite two lines of chemotherapy and stereotactic radiotherapy. On treatment with sorafenib and denosumab, a complete metabolic remission was achieved and is ongoing for over 18 months. Immunohistochemistry revealed an overexpression of RANK and RANKL in the patient's primary tumour. Discussion: This is the first report of activity achieved by the combination of the tyrosine kinase inhibitor sorafenib and the RANKL inhibitor denosumab in a patient with osteosarcoma. It confirms preclinical data on RANK/RANKL inhibition in osteosarcoma and could serve as a hypothesis-generating approach for clinical trials in this patient population.
© 2014 S. Karger AG, Basel
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References
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EURAMOS 1: A randomized trial of the European and American Osteosarcoma Study Group to optimize treatment strategies for resectable osteosarcoma based on histological response to pre-operative chemotherapy (ISRCTN67613327).
External Resources
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- Mei J, Zhu X, Wang Y, Wang Z: VEGFR, RET and RAF/MEK/ERK pathway take part in the inhibition of osteosarcoma MG63 cells with sorafenib treatment. Cell Biochem Biophys 2014;69:151-156.
Article / Publication Details
Received: August 31, 2014
Accepted: November 12, 2014
Published online: December 17, 2014
Issue release date: March 2015
Number of Print Pages: 4
Number of Figures: 2
Number of Tables: 0
ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)
For additional information: https://www.karger.com/OCL
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