Monday, September 2, 2013

DENOSUMAB IN CARCINOMA PROSTATE WITH BONY METASTASES

The patients with carcinoma prostate  or any solid tumor with bony metastases will have a cascade of events due to release of some substances from the tumor cells.These substances will lead to stimulation of osteoclasts and resorption of bones.Eventually the bone becomes brittle and skeletal related events (SRE) take place.  

There is a protein RANKL which acts like a ligand in bone resorption.The new molecule Denosumab is the first monoclonal antibody approved by the FDA in treatment of osteoporosis and bony metastases due to solid tumors.
As shown above the denosumab inhibits the RANKL and prevents the vicious cycle of the vents in bone removal.Thus the bone retains its strength.
We give this drug in metastatic carcinoma prostate to prevent the SREs.The dosage is 120 mg(1.7 ml) given subcutaneously every 4 weeks.

The most common side effects are altered immune response leading to UTI and respiratory tract infections, hypocalcemia, skin rashes and constipation etc.
The Denosumab is effective as Zoledronic acid in prevention of skeletal related events and perhaps better in prevention of first SRE.The one more advantage of the monoclonal antibody is that its dose need not be altered in patients with decreased renal function.We avoid Zoldronic acid in patients with altered renal profile.Most of the patients with Hormone Refractory Carcinoma Prostate have  upper tract changes and deranged renal function.So this aspect of Denosumab gives us leverage in treating such patients for prevention of SRE.    
     

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