title: 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.
authors: Department of Nuclear Medicine, Republic Specialized Center of Surgery, Tashkent, Uzbekistan.
authors: Nigora
authors: N
authors: Rasulova
authors: Vladimir
authors: V
authors: Lyubshin
authors: Dauranbek
authors: D
authors: Arybzhanov
authors: Valery
authors: V
authors: Krylov
authors: Marat
authors: M
authors: Khodjibekov
keywords: Bone metastases; Sm-153 systemic radionuclide therapy; Xgeva (Denosumab)
references: Calcif Tissue Int. 2000 Feb;66(2):100-3
references: 10652955
references: N Engl J Med. 2006 Feb 23;354(8):821-31
references: 16495394
references: J Clin Oncol. 2003 Feb 15;21(4):679-89
references: 12586806
references: J Clin Invest. 1999 Jan;103(2):197-206
references: 9916131
references: J Nucl Med. 1987 Apr;28(4):495-504
references: 3572535
references: J Nucl Med. 1994 Jan;35(1):63-9
references: 7505819
references: Oncology (Williston Park). 2009 Dec;23(14 Suppl 5):9-15
references: 20128323
references: J Urol. 2009 Aug;182(2):509-15; discussion 515-6
references: 19524963
references: J Biol Chem. 2002 Jul 5;277(27):24571-8
references: 11964407
references: Cancer Cell. 2003 Jun;3(6):537-49
references: 12842083
references: J Clin Invest. 1996 Oct 1;98(7):1544-9
references: 8833902
references: Cancer Res. 2002 Feb 1;62(3):917-23
references: 11830552
references: Nat Rev Cancer. 2003 Feb;3(2):110-6
references: 12563310
references: Nat Med. 1995 Sep;1(9):944-9
references: 7585222
references: N Engl J Med. 2008 Dec 25;359(26):2814-23
references: 19109576
references: Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6213s-6216s
references: 17062703
references: Lancet. 2011 Mar 5;377(9768):813-22
references: 21353695
references: N Engl J Med. 2004 Apr 15;350(16):1655-64
references: 15084698
references: J Bone Miner Res. 2005 Dec;20(12):2275-82
references: 16432953
references: J Clin Oncol. 2010 Dec 10;28(35):5132-9
references: 21060033
references: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10954-9
references: 12941866
references: Regul Pept. 2003 Apr 15;112(1-3):175-83
references: 12667640
references: Clin Exp Metastasis. 2003;20(2):171-80
references: 12705638
references: Cancer Res. 2005 Dec 1;65(23):11001-9
references: 16322249
references: Nat Rev Cancer. 2002 Aug;2(8):584-93
references: 12154351
references: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13909-14
references: 16172383