Chemotherapy for Rhabdomyosarcoma

Chemotherapy (chemo) is the use of drugs to treat cancer. Many chemo drugs for RMS are given intravenously (in a vein, IV) or sometimes by mouth as a pill or liquid. Chemo is absorbed into the bloodstream and goes throughout the body to destroy cancer cells.

Chemo is an important part of treatment for rhabdomyosarcoma (RMS). Even if it seems that all of the cancer was removed by surgery, without chemo it is likely to come back.

After surgery, any cancer cells that are still in the body can often be killed by chemo. If larger areas of tumor remain after surgery (or if surgery could not be done for some reason), chemo (along with radiation) can often shrink these areas. In some cases, it may make the tumor small enough that surgery can remove all of the tumor that is left.

Chemo drugs used to treat rhabdomyosarcoma

Doctors give chemo in cycles, which is usually treatment on one or two days in a row, followed by days off to give the body time to recover. For RMS, chemo is typically given once a week for the first few months, and then less often. The total length of treatment usually ranges from six months to a year or more.

Some drugs can be taken by mouth, but most are given IV (injected into a vein).

A combination of chemo drugs is used to treat patients with RMS. Which drugs are used will often depend on which risk group the patient is in.

For people in the low-risk group, the main combinations of drugs used are:

• VA: vincristine and dactinomycin (also known as actinomycin-D)
• VAC: vincristine, dactinomycin, and cyclophosphamide

Doctors are currently studying mutations in tumor genes in low-risk RMS. These gene changes may be able to predict which low-risk RMS tumors can be cured with less chemo and which low-risk tumors may behave more like intermediate-risk RMS and need more chemo.

For the intermediate-risk group, the most common regimen is:

• VAC: vincristine, dactinomycin, and cyclophosphamide
• VAC/VI: vincristine, dactinomycin, and cyclophosphamide, alternating with vincristine and irinotecan

Studies adding other chemo drugs to VAC or VAC/VI have not yet improved the outlook for people with intermediate-risk RMS. Current research is focused on finding the best dose of cyclophosphamide and whether or not maintenance chemo treatment improves the outlook for these people. Maintenance chemo is giving chemo treatments for a longer period of time, usually with lower doses.

For the high-risk group (which includes those with metastatic disease), the most common regimen is VAC. Because these cancers can be hard to treat, doctors have studied the use of more intense chemo in clinical trials. Unfortunately, studies of other chemo drugs and higher doses of chemo have not been found to be better than VAC, and they can cause more side effects.

Most doctors recommend that people in the high-risk group be treated in a clinical trial testing new drugs and drug combinations. High-risk RMS clinical trials are testing strategies like using vinorelbine chemo and longer treatments (maintenance chemo) to improve outcomes.

Possible side effects

Chemo drugs affect cells that grow fast. While cancer cells grow fast, other healthy cells in the body do too, for example blood-forming cells, hair cells, and cells that make up the lining of our gut. Damage caused by these drugs on fast-growing healthy cells results in side effects. The side effects depend on the type and doses of drugs, and the length of time they are given.

General side effects of chemo

 Side effects common to many chemo drugs include:

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

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 infections (from having too few white blood cells, called leukopenia)
• Easy bruising or bleeding (from low platelets, called thrombocytopenia)
• Fatigue (from low red blood cells, called anemia)

Most of these side effects tend to go away once treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Be sure to tell your doctor or nurse about side effects and talk about medicines to help treat them.

Side effects of certain drugs

Along with the risks above, some chemo drugs can have specific side effects. For example:

• Cyclophosphamide and ifosfamide can damage the bladder, causing blood in the urine. The risk of this happening can be lowered by giving the drugs with plenty of fluids and with a drug called mesna, which helps protect the bladder. This drug can also damage the ovaries or testicles, which could affect fertility (the ability to have children). Talk to your cancer care team about the risks of infertility with treatment, and ask if there are options for preserving fertility.
• Vincristine can cause nerve damage (neuropathy). Some patients may have tingling, numbness, weakness, or pain, particularly in the hands and feet. For example, some people develop a condition called foot drop, which can make it difficult to lift the front part of the foot. This may make it hard to walk, but physical therapy and braces can help. Often symptoms will get better when treatment ends, but it may not go away completely.
• Some chemo drugs can also increase the risk of developing a second type of cancer, usually a form of leukemia, years after the RMS is cured. While this is a serious risk, it is not common, and the small increase in risk has to be weighed against the importance of chemotherapy in treating RMS.

For more on some of these possible long-term side effects, see After Rhabdomyosarcoma Treatment.

Chemotherapy for relapsed or recurrent RMS

Chemotherapy (chemo) is one of the most commonly offered treatments when RMS recurs. The type and dose of chemo depends on what treatments have been tried before. For example, a child who had low-risk RMS initially might receive chemo similar to what is recommended for intermediate-risk RMS if it recurs. For people with higher-risk RMS that recurs, other combinations of chemo drugs may be recommended. This could include chemo not used in initial treatment or, in rare cases, high doses of chemotherapy followed by a stem cell transplant. Other treatments like immunotherapy and CAR-T therapy are also being studied for use in RMS. However, these are investigational and may only be available as a part of a clinical trial.