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.