As researchers have learned more about the molecular and genetic changes in cells that cause cancer, they have been able to develop newer drugs that specifically target some of these changes. These drugs, often called targeted therapy drugs, work differently from standard chemotherapy (chemo) drugs and have different side effects. Targeted drugs are especially important in diseases such as chordomas and other bone cancers, where chemo has not been very useful.
Some chordomas have gene defects (mutations) that make proteins that signal the cells to grow. These genes are called c-kit, PDGFRA, and PDGFRB. The drug imatinib (Gleevec®) is a targeted therapy drug that can block the signals from these genes. This can make some tumors stop growing or even shrink a little. Imatinib is used to treat chordomas that have spread or have come back after treatment. Imatinib has been used to treat chordomas for several years, but it isn’t approved by the Food and Drug Administration to treat this type of cancer. It is approved to treat more common cancers.
This drug is given as a pill, taken with food once a day. Common side effects are mild and can include diarrhea, nausea, muscle pain, and fatigue. These are generally mild. Some people taking the drug have itchy skin rashes. Fluid buildup around the eyes, feet, or abdomen can also be a problem.
Denosumab (Xgeva®) is a monoclonal antibody (a man-made version of an immune system protein) that binds to a protein called RANK ligand. RANK ligand normally tells cells called osteoclasts to break down bone, but when denosumab binds to it, that action is blocked. In patients with giant cell tumors of bone that have either come back after surgery or cannot be removed with surgery, denosumab can help shrink tumors for a while.
To treat giant cell tumors, this drug is injected under the skin (sub-q or SQ), weekly for 4 weeks, and then every 4 weeks. Often, it can take months to see tumor shrinkage.
Most side effects are mild and can include body aches, headache, and nausea. A rare but very distressing side effect of denosumab is damage to the jawbone called osteonecrosis of the jaw (ONJ). ONJ often appears as an open sore in the jaw that won’t heal. It can lead to loss of teeth or infections of the jaw bone. Doctors don’t know why this happens, but it can be triggered by having a tooth removed while taking the drug. The best treatment is also unclear, other than to stop denosumab. Maintaining good oral hygiene by flossing, brushing, making sure that dentures fit properly, and having regular dental check-ups may help prevent this. Most doctors recommend that patients have a dental checkup and have any tooth or jaw problems treated before they start taking this drug.
For more general information about drugs that are considered targeted therapy, see our document Targeted Therapy.
Last Revised: 01/21/2016