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.
Keywords
Bone metastases - Sm-153 systemic radionuclide therapy - Xgeva (Denosumab)
