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RANK Ligand Blockade with Denosumab in Combination with Sorafenib in Chemorefractory Osteosarcoma: A Possible Step Forward?

Richard Cathomas, Christian Rothermundt, Beata Bode, Bruno Fuchs, Roger Von Moos & Michael Schwitter

abstract UNASSIGNED
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.
   
citation Cathomas R, Rothermundt C, Bode B, Fuchs B, Von Moos R, schwitter m. RANK Ligand Blockade with Denosumab in Combination with Sorafenib in Chemorefractory Osteosarcoma: A Possible Step Forward?. Oncology 2014; 88:257-260.
   
type journal paper/review (English)
date of publishing 17-12-2014
journal title Oncology (88/4)
ISSN electronic 1423-0232
pages 257-260
PubMed 25531914
DOI 10.1159/000369975