Targeted Therapy and Other Drugs for Bone Cancer

As researchers have learned more about the gene changes inside cells that can lead to bone cancer, they have developed newer drugs that specifically target some of these changes. These targeted drugs work differently from standard chemotherapy (chemo) drugs, and they tend to have different side effects.

Targeted drugs are especially important in treating types of bone cancer where chemo has not been very useful, such as chordomas.

Other types of non-chemo drugs that can be used to treat some types of bone cancers include bone-directed drugs and immunotherapy drugs.

The information here focuses on primary bone cancers (cancers that start in bones) that most often are seen in adults. Information on Osteosarcoma, Ewing Tumors (Ewing sarcomas), and Bone Metastasis is covered separately.

Targeted drugs for bone cancer

The targeted drugs used to treat some types of bone cancers are known as kinase inhibitors. Kinases are proteins in the cell (or on its surface) that normally relay signals (such as telling the cell to grow). Blocking certain kinases can help stop or slow the growth of some tumors.

These drugs are used most often to treat chordomas that have spread or have come back after treatment. Some of these drugs might also be used to treat advanced chondrosarcomas. 

Examples of kinase inhibitors include:

• Imatinib (Gleevec)
• Dasatinib (Sprycel)
• Sunitinib (Sutent)
• Erlotinib (Tarceva)
• Lapatinib (Tykerb)
• Sorafenib (Nexavar)
• Regorafenib (Stivarga)
• Pazopanib (Votrient)

These drugs are pills, typically taken once or twice a day. 

The side effects of these drugs can vary, based on which one is being used, and can include things like diarrhea, nausea, muscle pain, and fatigue. Some of these drugs can cause itchy skin rashes or fluid build-up around the eyes, feet, or belly.

Drugs that affect bone cells

Denosumab (Xgeva) is a drug known as a RANKL inhibitor. The RANKL protein normally tells cells called osteoclasts to break down bone. By binding to RANKL denosumab can block this.

This drug can be used to treat giant cell tumors of bone that have either come back after surgery or cannot be removed with surgery.

This drug is injected under the skin (sub-q or SQ). Often, the tumor can take months to shrink.

Most side effects are mild and can include body aches, fatigue, diarrhea, and nausea. A rare but very serious side effect of denosumab is damage to the jawbone, called osteonecrosis of the jaw (ONJ). This can lead to loss of teeth and/or infections of the jaw bone. ONJ can be triggered by having dental work while taking the drug. 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 check-up and have any tooth or jaw problems treated before they start taking this drug.

Immunotherapy drugs for bone cancer

Immunotherapy drugs help the body’s own immune system recognize and attack cancer cells.

Pembrolizumab (Keytruda)

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoint” proteins on immune cells, which act like switches that need to be turned on (or off) to start an immune response. Cancer cells sometimes exploit these checkpoints to avoid being attacked by the immune system.

Pembrolizumab targets the PD-1 checkpoint protein on immune system cells called T cells. This protein normally helps keep these cells from attacking other cells in the body. By blocking PD-1, this drug boosts the immune response against cancer cells. This can shrink some tumors or slow their growth.

This drug can be used in some people with advanced bone cancer if the cancer cells have certain types of gene changes.

Pembrolizumab is given as an intravenous (IV) infusion, typically once every 3 or 6 weeks.

Possible side effects of this drug can include feeling tired or weak, cough, nausea, itching, skin rash, loss of appetite, muscle or joint pain, shortness of breath, and constipation or diarrhea.

Other, more serious side effects occur less often:

Infusion reactions: This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting this drug.

Autoimmune reactions: This drug works by basically removing one of the safeguards on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making (endocrine) glands, kidneys, skin, or other organs.

Interferon alfa-2b

Interferons are a family of substances naturally made by our immune system. Interferon alfa-2b may be used to treat giant cell tumors of the bone that have come back after treatment or that have spread.

This drug is most often given daily as an injection under the skin. It can also be injected into a muscle or vein.

Interferon can cause significant side effects. These include "flu-like" symptoms like muscle aches, bone pain, fever, headaches, fatigue, nausea, and vomiting. Patients taking this drug might have problems thinking and concentrating. Interferon can also lower blood cell counts. These effects continue as long as the drug is used, but can become easier to tolerate over time. Still, some patients find it hard to deal with these side effects every day and may need to stop treatment because of them.

For more information about drugs that help the immune system attack cancer, see Immunotherapy.