Burden of giant-cell tumor of the bone reduced by denosumab

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When patients with giant-cell tumor of the bone were treated with denosumab, which is a drug targeted against a protein that promotes bone destruction, the number of tumor giant cells decreased and new bone formation increased. This study was recently published in Clinical Cancer Research.

“Giant-cell tumor of the bone is a rare tumor that affects mostly young people,” said Sant P. Chawla, MD, director of the Santa Monica Oncology Center, Santa Monica, California. “Radical surgery is currently the only treatment option. In our study, the use of denosumab allowed patients to avoid radical surgery and prevented recurrence. We hope that in the future, its use may make it possible to avoid surgery completely.”

Giant-cell tumor of the bone is a benign tumor that is characterized by giant cells that are positive for the protein RANK ligand, which helps to promote bone destruction. The RANK ligand is inhibited by denosumab. To date, the only treatment for giant-cell tumor of the bone is surgery, but it often results in recurrent disease or significant morbidity, such as amputation. Also, 25% to 30% of patients with this tumor need joint replacements.

This phase II study treated 20 adult patients with recurrent or unresectable giant-cell tumor of the bone with subcutaneous denosumab every 4 weeks. Following the treatment, giant cells were reduced by 90% or more in all 20 of the patients, which indicates that their tumor burden was reduced. New bone growth occurred in 65% of patients in areas where the RANK ligand had previously caused bone destruction.

“A majority of patients with giant-cell tumor of the bone are young and have to get joint replacements, which last 15 to 20 years before a repeat surgery is needed,” stated Chawla. “Now, we hopefully can do minimal surgery, avoiding a joint replacement and recurrence.”

A much larger, multinational study is currently enrolling patients to further evaluate denosumab for giant-cell tumor of the bone. Furthermore, Chawla hopes to also evaluate using denosumab as a neoadjuvant treatment.

“In the future we hope to investigate giving the drug prior to surgery to see the effect it has, then remove the tumor and evaluate the pathological response,” Chawla said.
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