Chemotherapy and Other Drugs for Osteosarcoma

Chemotherapy (chemo) is the use of drugs to treat cancer. The drugs are usually given into a vein and can reach and destroy cancer cells throughout the body.

Chemo is an important part of the treatment for most people with osteosarcoma (although some patients with low-grade osteosarcoma might not need it). Most osteosarcomas don’t appear to have spread beyond the main tumor when they are first found. But in the past, when these cancers were treated with surgery alone, the cancer would often come back in other parts of the body, where it would be very hard to control. Giving chemo along with surgery helps lower the risk of these cancers coming back.

Most osteosarcomas are treated with chemo before surgery (known as neoadjuvant chemotherapy) for about 10 weeks. In some people with osteosarcoma in an arm or leg bone, this can shrink the tumor, which might help make surgery easier. Chemo is then given again after surgery (known as adjuvant chemotherapy) for up to a year.

Chemo in is given in cycles, with each period of treatment followed by a rest period to give the body time to recover. Each cycle typically lasts for a few weeks.

Chemo drugs used to treat osteosarcoma

The drugs used most often to treat osteosarcoma include:

• Methotrexate (given in high doses, along with leucovorin to help limit side effects)
• Doxorubicin (Adriamycin)
• Cisplatin or carboplatin
• Ifosfamide
• Cyclophosphamide
• Etoposide
• Gemcitabine

Usually, 2 or more drugs are given together. Some common combinations of drugs include:

• High-dose methotrexate, doxorubicin, and cisplatin (known as the MAP regimen), sometimes with ifosfamide. This is used more often in children, teens, and young adults.
• Doxorubicin and cisplatin. This is used more often in older adults.
• Ifosfamide and etoposide
• Ifosfamide, cisplatin (or carboplatin), and epirubicin

Many experts recommend that the drugs be given in very high doses when possible.

Before starting chemo, the doctor might advise putting a catheter (a thin, soft tube) into a large vein in the chest. This is sometimes called a venous access device (VAD) or central venous catheter (CVC). The catheter is inserted surgically while the patient is sedated (sleepy) or under general anesthesia (in a deep sleep). One end of the catheter stays in the vein, while the other end lies just under or outside the skin. This lets the health care team give chemo and other drugs and draw blood samples without having to stick needles into the veins each time. The catheter usually remains in place for several months and can make having chemo less painful. If such a device is used, the health care team will teach you how to care for it to reduce the risk of problems such as infections.

Side effects of chemo

Chemo drugs can cause side effects. Children tend to have less severe side effects from chemo than adults and often recover from side effects more quickly. Because of this, doctors can give them higher doses of chemo to try to kill the tumor.

The side effects of chemo drugs depend on the type, dose, and the length of time they are taken.

General side effects of chemo

• Nausea and vomiting
• Loss of appetite
• Diarrhea
• Hair loss
• Mouth sores

Chemo can damage the bone marrow, where new blood cells are made. This can lead to low blood cell counts, which can result in:

• Increased chance of infection (from a shortage of white blood cells)
• Bleeding or bruising after minor cuts or injuries (from a shortage of platelets)
• Fatigue or shortness of breath (from low red blood cell counts)

A major concern with chemo used to treat osteosarcoma is that it can lead to dangerously low white blood cell levels and an increased risk of serious infections. Because of this, drugs called growth factors (such as filgrastim, also known as G-CSF) may be given along with the chemo to help the body make new white blood cells as quickly as possible.

Most of the side effects above tend to go away after treatment is finished. Often there are ways to make these side effects less severe. For example, drugs can be given to help prevent or reduce nausea and vomiting, or to help get blood counts back to normal levels. Be sure to discuss any questions you have about side effects with the cancer care team, and tell them about any side effects so that they can be controlled.

Side effects of certain chemo drugs

Some side effects are specific to certain drugs. Many of these side effects are uncommon, but they are possible. Before treatment, ask your cancer care team about the possible side effects of the drugs you or your child will be getting.

• Ifosfamide and cyclophosphamide can damage the lining of the bladder, which can cause blood in the urine. The chance of this happening can be lowered by giving a drug called mesna during chemotherapy, along with plenty of fluids.
• Cisplatin and carboplatin can cause nerve damage (called neuropathy) leading to numbness, tingling, or pain in the hands and feet. This often goes away or gets better once treatment is stopped, but it might last a long time in some people. These drugs can sometimes affect hearing, especially of high-pitched sounds. Kidney damage can also occur after treatment. Giving lots of fluid before and after the drug is infused can help prevent this.
• Etoposide can also cause nerve damage. It can also increase the risk of later developing acute myeloid leukemia (AML), a cancer of white blood cells. Fortunately, this is not common.
• High-dose methotrexate can damage the white matter of the brain (called leukoencephalopathy) and can also affect the liver and kidneys. Before starting high-dose methotrexate, medicines are given to help protect the kidneys. Methotrexate blood levels may be checked to see how much leucovorin (also called folinic acid) should be given to help limit any damage to normal tissues.
• Doxorubicin (Adriamycin) can damage the heart muscle. The risk of this goes up with the total amount of the drug that is given, so doctors are careful to limit the total dose. Your (child’s) doctor may order a heart function test (such as an echocardiogram) before and during treatment to see if this drug is affecting the heart. A drug called dexrazoxane may be given along with the chemo to help lessen the possible damage.

Some chemo drugs can affect your (child’s) ability to have children (fertility) later in life. Ask the cancer care team about the possible effects of treatment on fertility, and ask if there are options for preserving fertility, such as sperm banking or egg preservation.

The doctors and nurses will watch closely for side effects. Don’t hesitate to ask the cancer care team any questions about side effects.

For more information on the possible late or long-term side effects of chemo, including infertility and second cancers, see Late Effects of Childhood Cancer Treatment.

Tests to check for side effects of chemo: Before each treatment, lab test results will be checked to be sure the liver, kidneys, and bone marrow are working well. Other tests might be done during and after treatment as well.

• The complete blood count (CBC) checks levels of white blood cells, red blood cells, and blood platelets. These will be watched closely during and after chemo. The white blood cells and platelets usually reach their lowest point about 2 weeks after chemo is given, though this can occur earlier with high-dose regimens.
• Blood chemistry tests measure certain blood chemicals that tell doctors how well the liver and kidneys are working. Some chemo drugs can damage these organs.
• An audiogram might be done to check hearing, which can be affected by certain chemo drugs.
• If doxorubicin is to be given, tests such as an echocardiogram (an ultrasound of the heart) may be done before and during treatment to check heart function.

For more information, see Chemotherapy.

Other drugs to treat osteosarcoma

If chemo drugs are no longer helpful, other types of drugs might be an option in some situations.

Targeted therapy drugs

Doctors are now studying newer drugs that target specific parts of tumor cells (or nearby cells) as a way to treat osteosarcoma. These targeted drugs work differently from standard chemo drugs. They might be helpful sometimes when chemo drugs are no longer working.

For example, regorafenib (Stivarga), sorafenib (Nexavar), and cabozantinib (Cabometyx) are drugs that affect a tumor’s ability to develop new blood vessels, which it needs to grow. These drugs have been shown to help some people with osteosarcoma in early studies. Although these drugs are not yet FDA-approved to treat osteosarcoma, they are approved to treat other types of cancer, and trying one of them might be an option if standard chemo drugs are no longer helpful.

Common side effects of these drugs can include fatigue, loss of appetite, hand-foot syndrome (redness and irritation of the hands and feet), high blood pressure, weight loss, diarrhea, and abdominal (belly) pain.
Less common but more serious side effects can include problems with blood flow to the heart, bleeding, abnormal thyroid test results, and perforations (holes) in the stomach or intestines.

For more on this type of treatment, see Targeted Therapy.

Radioactive drugs (radiopharmaceuticals)

Drugs that include a radioactive element can sometimes be helpful in people with advanced osteosarcoma. These drugs are injected into the blood and travel to the bones, where they give off small amounts of radiation that can help slow tumor growth and treat symptoms such as pain. For more information, see Radiation Therapy for Osteosarcoma.