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Oncology. 2015;88(4):257-60. doi: 10.1159/000369975. Epub 2014 Dec 17.

RANK ligand blockade with denosumab in combination with sorafenib in chemorefractory osteosarcoma: a possible step forward?

Author information

1
Division of Oncology/Haematology, Kantonsspital Graubünden, Chur, Switzerland.

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.

PMID:
25531914
DOI:
10.1159/000369975
[Indexed for MEDLINE]
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