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Chemotherapy (chemo) is the use of anti-cancer drugs to treat cancer. Chemo can be given in different ways to treat retinoblastoma.

Systemic chemotherapy

Chemo drugs can be injected into a vein (IV) or given by mouth. These drugs enter the bloodstream and reach throughout the body. This is known as systemic chemotherapy.

Systemic chemo is given in cycles, with each treatment followed by a rest period to give the body time to recover. Each chemo cycle typically lasts for a few weeks, and the total length of treatment is often several months.

Some of the chemo drugs used to treat retinoblastoma include:

• Carboplatin
• Cisplatin
• Vincristine
• Etoposide
• Cyclophosphamide
• Topotecan
• Doxorubicin

Most often, 2 or 3 drugs are given at the same time. A standard combination is carboplatin, vincristine, and etoposide, although for very small tumors, only carboplatin and vincristine may be enough. Other drugs might be used if these are not effective.

Intra-arterial chemotherapy

Sometimes instead of systemic chemotherapy, the chemo is injected directly into the ophthalmic artery, the main artery that supplies blood to the eye. In this newer technique, a very thin catheter (a long, hollow, flexible tube) is inserted into a large artery on the inner thigh and slowly threaded through the blood vessels all the way up into the ophthalmic artery. (This is done with the child asleep under general anesthesia.) The chemo is then infused into the artery. The drug used most often is melphalan, but other drugs such as carboplatin and topotecan can also be used. This process may then be repeated every few weeks, depending on how much the tumor shrinks.

Because the chemo is put directly into the artery feeding the eye, doctors can use much smaller doses of chemo drugs (less than 10% of the doses used for systemic chemo). Therefore, there are fewer side effects from the chemo.

Results so far with this technique in eyes with advanced tumors have been promising, generally with good tumor control and few side effects. In many cases it has allowed doctors to save an eye that otherwise would have needed to be removed.

Intravitreal chemotherapy

In this newer approach, a tiny needle is used to inject a chemo drug (typically melphalan or topotecan) directly into the vitreous humor, the jelly-like substance inside the eye. This is sometimes used (along with systemic or intra-arterial chemo) to treat tumors that are widespread within the eye and have not been helped by other treatments. 

Ways chemotherapy is used

Chemo may be used in different situations:

• Chemo can be used as the first treatment to shrink some tumors that have not spread outside the eye. This is called chemoreduction. These tumors can then be treated more effectively with focal therapies such as laser therapy, cryotherapy, or brachytherapy.
• Chemo is sometimes used when the eye has already been treated or removed, but the tumor has extended into some areas in the eye that make it more likely to have spread. This type of treatment is called adjuvant chemotherapy.
• Systemic chemo is also used to treat children whose retinoblastoma has spread outside the eye, a much more critical situation. If the cancer has spread to the brain, chemo may also be given directly into the cerebrospinal fluid that surrounds it. (This is known as intrathecal chemotherapy.) Tumors outside the eye may shrink for a time with standard doses of chemo, but they will usually start growing again. For this reason, if the cancer has spread to other parts of the body, doctors recommend giving more intense chemo, usually along with a stem cell transplant.

Possible side effects of chemo

Systemic chemo: Chemo drugs can affect cells in the body other than cancer cells, which can lead to side effects.

The side effects of chemo depend on the types and doses of drugs used, and how long they are given. Possible short-term side effects include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Diarrhea or constipation
• Increased chance of infections (from having too few white blood cells)
• Easy bruising or bleeding (from having too few blood platelets)
• Fatigue (from having too few red blood cells)

Most of these side effects go away after 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 discuss any questions about side effects with your child’s cancer care team, and let them know if your child has side effects so they can be managed.

Along with the effects listed above, certain chemo drugs can cause specific side effects. For example:

• Cisplatin and carboplatin can affect the kidneys. Giving the child plenty of fluids during treatment can help reduce this risk. These drugs can also cause hearing loss in young children, especially in babies younger than 6 months. Your child’s doctor may check your child’s hearing with tests during or after treatment. When carboplatin is injected directly into the tissues near the eye (periocular chemotherapy), it can cause redness and swelling in the area.
• Vincristine can damage nerves. Some children may feel tingling and numbness, particularly in their hands and feet.
• Some chemo drugs can increase the risk of developing a cancer of white blood cells known as acute myeloid leukemia (AML) later in life. Fortunately, this is not common.
• Doxorubicin can damage the heart. The risk of this happening goes up with the total amount of the drug given. Doctors try to limit this risk as much as possible by not giving more than the recommended doses and by checking the heart with an echocardiogram (an ultrasound of the heart) during treatment.
• Cyclophosphamide can damage the bladder, which can cause blood in the urine. The risk of this can be lowered by giving this drug along with plenty of fluids and with a drug called mesna, which helps protect the bladder. Cyclophosphamide can also lower the chances of having children in the future.

Intra-arterial chemo: Much lower doses of chemo are used in this approach, so the side effects tend to be limited to the eye area. Possible side effects include:

• Swelling around the eye
• Detachment of the retina from the back of the eye
• Bleeding inside the eye
• Weakening of the muscles that move the eye
• Drooped eyelid
• Loss of eyelashes

Possible long-term side effects are not yet clear, as this technique is still fairly new. Treatment might affect the small blood vessels in and around the eye, although it’s not yet known if this might affect vision as the child gets older. This approach also exposes the child to some radiation, because real time x-rays are used to help guide the catheter into place. It’s not yet clear if (or how much) this might raise cancer risk later in life. 

Intravitreal chemo: As with intra-arterial chemo, the side effects from this newer technique seem to be limited to the eye and nearby areas. Each treatment might damage the retina slightly, which might affect vision.

In the past, there was concern that placing a needle into the eye to give the chemo might open a small hole that could allow tumor cells to spread outside of the eye. However, studies have found that this risk is very low, and doctors now use techniques that lower this risk even further.