Chemotherapy is the use of drugs for treating cancer. Chemotherapy is systemic therapy. This means that the drug enters the bloodstream and circulates to reach and destroy the cancer cells throughout the body. This makes chemotherapy useful for osteosarcoma that has spread through the bloodstream to the lungs and/or other organs or has a high risk of doing so. Some patients with low-grade osteosarcoma may not benefit from chemotherapy, though the majority of osteosarcoma patients do. Most cases of osteosarcoma are treated with chemotherapy given before surgery (neoadjuvant chemotherapy) and after surgery (adjuvant chemotherapy). People with high-grade osteosarcoma whose tumors responded well to chemotherapy before surgery should get the same chemotherapy after surgery for several months. People whose tumors responded poorly usually will get different chemotherapy after surgery.

The drugs used currently to treat osteosarcoma include:

• methotrexate -- given in very high doses and followed with leucovorin, which neutralizes the drug and prevents serious side effects
• doxorubicin (Adriamycin)
• cisplatin or carboplatin
• etoposide
• ifosfamide
• cyclophosphamide
• actinomycin D (dactinomycin)
• bleomycin

Usually, several drugs (2 or 3) are given together. For example, a very common combination is doxorubicin and cisplatin. Other combinations are dactinomycin, bleomycin and cyclophosphamide, or ifosfamide and etoposide.

The most commonly used regimen for treating osteosarcoma includes high-dose methotrexate, doxorubicin, and cisplatin. Ifosfamide is also very commonly added to this regimen, either alone or in combination with etoposide. A recent study, however, did not find any advantage to adding ifosfamide. Many experts recommend that the drugs be given in very high doses, which can temporarily suppress formation of new blood cells. In these cases, other drugs called growth factors (such as neupogen), are need to stimulate blood cell formation so the patient’s blood counts recover as quickly as possible (see below).

Side effects of chemotherapy

Chemotherapy kills cancer cells, but it will also damage some normal cells. Therefore, careful attention is given to avoiding or minimizing side effects. The side effects of chemotherapy depend on the type of drugs, the amount taken, and the length of time they are taken.

Temporary side effects might include nausea and vomiting, loss of appetite, loss of hair, and mouth sores. If you or your child has any side effects, it is important to tell your cancer care team because medicines can be taken to prevent or control them

Because chemotherapy can damage the blood-producing cells of the bone marrow and lymph nodes, patients may have low blood cell counts. Low blood cell counts can result in:

• increased chance of infection (due to a shortage of white blood cells)
• bleeding or bruising after minor cuts or injuries (due to a shortage of platelets)
• fatigue or shortness of breath (due to low red blood cell counts)

Chemotherapy may rarely cause a second type of cancer (such as leukemia), years after the osteosarcoma is cured. However, the importance of chemotherapy in treating osteosarcoma far outweighs this risk.

Infertility is not a common side effect of the treatment for osteosarcoma, but it can occur. Women may experience changes in menstrual periods, but normal monthly cycles usually return after chemotherapy ends. Boys and men may lose the ability to make sperm. This usually returns, but the sperm count may remain low. If you have concerns, you might want to ask the cancer care team about sperm banking.

Some side effects are specific to particular drugs. It’s important to note that many of the serious side effects are rare, but possible. Discuss these with your cancer care team if you have concerns before treatment.

Ifosfamide and cyclophosphamide may cause hemorrhagic cystitis (bladder inflammation and blood in the urine) and kidney damage, with loss of salt and minerals in the urine. After ifosfamide or cyclophosphamide, a drug called mesna will be given to protect the bladder.

Cisplatin may produce severe and delayed nausea for several days, problems with hearing loss (especially high pitched sounds) or even deafness, and kidney damage. It can also cause nerve damage, which is mainly felt as numbness and tingling of the arms and legs.

High-dose methotrexate may cause liver damage, sores in the mouth and digestive tract, leukoencephalopathy (damage to the white matter of the brain), and reversible kidney damage. Before starting high-dose methotrexate, a bicarbonate solution will be added to the intravenous (IV) fluids to keep the urine alkaline (a ph of 7 or above). This helps protect the kidneys. Methotrexate blood levels may be checked to see how much folinic acid (also called leucovorin) should be given to stop any damage to normal tissues. Folinic acid is started 24 hours after the high-dose methotrexate to neutralize it. The high-dose methotrexate would be too toxic without “folinic acid rescue.” The folinic acid will be continued until the methotrexate level is safe.

Doxorubicin (Adriamycin) may cause heart damage and may also induce second cancers. If the drug leaks from the vein into the surrounding tissues, the skin may be burned.

The doctors and nurses will watch you closely for side effects. Most side effects can be treated, but preventing significant side effects is more important. Most, if not all, of these side effects will eventually stop after the treatment is over. Do not hesitate to ask your cancer care team any questions about side effects. .

Tests to check for side effects of chemotherapy

Before giving these drugs, your doctor will check your laboratory test results to be sure your liver, kidney, and bone marrow (which produces the cells in the blood) are functioning well.

The complete blood count (CBC) includes counts of white blood cells (WBCs), red blood cells (RBCs), and blood platelets. WBCs fight infections, so it is important to know the white blood cell count before chemotherapy starts. Platelets are small cells that plug up holes in blood vessels. If the platelet count is low, excessive bleeding could occur during surgery or as a result of even minor injuries. RBCs carry oxygen in the bloodstream. Chemotherapy can lower the numbers of all blood cells checked on a CBC, so blood counts will be watched closely before and after chemotherapy. The cells usually reach their lowest point about 2 weeks after chemotherapy is given, though this occurs earlier with high-dose regimens.

Routine blood chemistry panels measure certain blood chemicals that tell doctors how well the liver and the kidneys are working. Some drugs used in chemotherapy can damage the kidneys and liver.

An audiogram measures the patient's ability to hear. Some drugs used in chemotherapy may affect hearing.

If doxorubicin is to be given, an echocardiogram is done to check heart function.

Last Medical Review: 01/14/2009
Last Revised: 01/14/2009