The monoclonal antibody denosumab has now been approved in a new strength, under the trade name Xgeva, for use in patients with metastasized cancer. Denosumab helps prevent bone-related events, such as bone fractures, spinal cord compression, or bone pain severe enough to require radiation or surgery. Denosumab was originally approved in June 2010 under the trade name Prolia for women with osteoporosis who are at high risk for bone fractures. A higher dosage of denosumab is required to prevent bone-related events in cancer patients.
Monoclonal antibodies are considered targeted therapy, which means that they seek out specific cells on which to act. In the case of Xgeva, the cells that are targeted express a protein called human RANKL (receptor activator of nuclear factor κB ligand), which is involved in cancer-related bone destruction. Xgeva has a different mechanism of action than the other drugs approved for this use, such as zoledronic acid (Zometa, Reclast) and pamidronate disodium (Aredia), which are both bisphosphonates. (Bisphosphonates inhibit the osteoclastic resorption of bone by binding to it; they also inhibit the increased osteoclastic activity and skeletal calcium release induced by factors released by tumors.)
Clinical trials that led to the approval of Xgeva found it to be superior to zoledronic acid in delaying the onset of a bone-related event in patients with metastatic breast or prostate cancer. Xgeva wasn't found to be superior to zoledronic acid in patients with solid tumors such as lung cancers, kidney cancer, or multiple myeloma.
Serious adverse effects of Xgeva include hypocalcemia and, like the bisphosphonates, osteonecrosis of the jaw (a severe disease resulting from reduced blood flow to areas of the jaw and exposed jaw bone, causing pain, swelling, numbness, or infection). Unlike the bisphosphonates, Xgeva doesn't increase the risk of renal failure. Nurses should monitor calcium levels in patients receiving Xgeva and assess for any new onset of jaw pain. To read the Food and Drug Administration news release on the approval of denosumab in its new strength, go to http://bit.ly/b4HcWb.