Effectiveness of Bone Metastases Treatment by Sm-153 Oxabifore in Combination with Monoclonal Antibody Denosumab (Xgeva): First Experience

Abstract

Breast and prostate cancer have a propensity to metastasize to bones and cause osteolysis and abnormal new bone formation. Metastases locally disrupt normal bone remodeling. Although metastases from prostate cancer have been classified as osteoblastic based on the radiographic appearance of the lesion, data gleaned from a rapid autopsy program indicate that the same prostate cancer patient may have evidence of both osteolytic and osteoblastic disease as shown by histologic examinations. Thus, bone metastases are heterogeneous, requiring combined treatment targeting on both osteolytic and osteoblastic lesions. While Samarium-153 (Sm-153) oxabifore treatment is widely used for the relief of pain in patients with osteoblastic metastatic bone lesions, Xgeva (Denosumab) is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. It is a fully human monoclonal antibody that has been designed to target receptor activator of nuclear factor-kB ligand (RANKL), a protein that acts as the primary signal to promote bone removal. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. The main objectives of the current pilot study were to estimate the effectiveness of bone metastases treatment by a combination of Sm-153 oxabifore and Xgeva (Denosumab). Five patients (four female and one male, aged 35-64, mean age 50.8) with multiple skeletal metastases from prostatic carcinoma (1) and breast carcinoma (4) were studied. Their mean objective pain score according to visual analog scoring system on a 1-10 scoring system was 7.8 ± 0.5 (range 6-9). Sm-153 oxabifore was administered at the standard bone palliation dose of 37 MBq/kg body weight. Xgeva (Denosumab) was administered at a dosage of 120 mg every 4 weeks, with the monitoring of calcium level and administration of calcium, magnesium, and vitamin D. Whole body (WB) bone scan was performed before and 3 months after treatment in all patients. After Sm-153 oxabifore administration, pain relief occurred within 4.4 ± 1.25 days (range 2-9 days) and the objective pain score decreased to 0.2 ± 0.2 (range 0-1). There was statistically significant difference found, according to the pain score system, before and after treatment (P < 0.0001). WB bone scan showed that in one patient, there was significant reduction in the number and intensity of bone metastases, and in four patients, there was no evidence of bone metastases found. Based on our first experience, combined treatment of bone metastases with Sm-153 oxabifore and Denosumab is effective and safe.

Bone health in breast cancer patients: A comprehensive statement by CECOG/SAKK Intergroup

“…Recently, the combination of Sm-153 oxabifore and denosumab proved highly effective in breast cancer patients with painful bone metastases and disease progression in spite of previous bisphosphonate therapy [68]. Pain relief occurred within 4.4 ± 1.25 days and the pain score decreased significantly from 7.8 at baseline to 0.2 (p < 0.0001) after six months of combined treatment.…”

Bone metastases treatment by Sm-153 oxabifore in combination with monoclonal antibody denosumab (Xgeva)

“…To the Editor, A recent report on "bone metastases treatment by samarium (sm)-153 oxabifore in combination with monoclonal antibody denosumab (Xgeva)" is very interesting. [1] Rasulova et al noted that "combined treatment of bone metastases with sm-153 oxabifore and denosumab is effective and safe. [1] " In fact, the combination is very interesting.…”

“…[1] Rasulova et al noted that "combined treatment of bone metastases with sm-153 oxabifore and denosumab is effective and safe. [1] " In fact, the combination is very interesting. A similar observation was also reported by Rasulova et al on another combination between sm-153 oxabifore and bisphosphonate.…”