Arsenic trioxide and Tretinoin

Arsenic trioxide is a chemotherapy drug. It is also called Trisenox or ATO.

Tretinoin belongs to a group of medicines called retinoids, these are similar to vitamin A. Tretinoin is also called ATRA or vesanoid.

The combination of arsenic trioxide and tretinoin is a treatment for a type of acute myeloid leukaemia called acute promyelocytic leukaemia (APL or APML).

You pronounce arsenic trioxide as ar-ss-nic try-oxide.

You pronounce tretinoin as tret-in-oh-in.

How does arsenic trioxide and tretinoin work?

Arsenic tretinoin works by speeding up the death of leukaemia cells and encouraging normal blood cells to develop properly. It does this by working on particular proteins within the cell.

Tretinoin treats promyelocytic leukaemia by encouraging the abnormal leukaemia cells to develop normally.

How do you have arsenic trioxide and tretinoin?

Into the bloodstream

You have arsenic trioxide as a drip into your bloodstream. You go into hospital to have treatment.

You have the drip over 2 hours. But if you have a reaction while having it you may have it more slowly over 4 hours.

You might have treatment through a long plastic tube that goes into a large vein in your chest. The tube stays in place throughout the course of treatment. This can be a:

• central line
• PICC line
• portacath

Taking capsules

Tretinoin is a capsule. You take the capsules twice a day. You doctor will tell you how many to take.

It is recommended that you take the capsules with a meal or very soon after.

You should take the right dose, not more or less.

Talk to your healthcare team before you stop taking a cancer drug or if you miss a dose.

How often do you have arsenic trioxide and tretinoin?

You may have arsenic trioxide to get rid of the leukaemia cells (induction treatment ) or to stop your leukaemia coming back (consolidation treatment ).

Induction treatment
In the first week you have arsenic trioxide once a day for 5 days. You then have it twice a week for the next 7 weeks.

You take tretinoin every day until there is no sign of leukaemia (complete remission) or for a maximum of 60 days.

Consolidation treatment
For consolidation you have 4 cycles of treatment . The first 3 cycles are 8 weeks long.

Cycle 4 of the consolidation is over 4 weeks.

Tests

You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver and kidneys are working.

Before treatment and regularly during the treatment you have a test of your heart called an ECG.

What are the side effects of arsenic trioxide and tretinoin?

Side effects can vary from person to person. They also depend on what other treatments you're having. 

When to contact your team

Your doctor, nurse or pharmacist will go through the possible side effects. They will monitor you during treatment and check how you are at your appointments. Contact your advice line as soon as possible if:

• you have severe side effects 

• your side effects aren’t getting any better

• your side effects are getting worse

Early treatment can help manage side effects better. 

We haven't listed all the side effects here. Talk to your healthcare team if you have any new symptoms that you think might be a side effect of your treatment.

Remember it is very unlikely that you will have all of these side effects. But you might have some of them at the same time.

Common side effects

These side effects happen in more than 10 in 100 people (more than 10%). You might have one or more of them. They include:

Fast release of immune substances into your blood

Let your team know straight away if you develop symptoms such as difficulty in breathing, a cough, chest pain or high temperature.

This could be a sign that you have differentiation syndrome. This is when you have a fast release of immune substances (cytokines) into your blood. It needs to be treated quickly as it can be life threatening. 

Tiredness and weakness (fatigue) 

Tiredness and weakness (fatigue) can happen during and after treatment. Doing gentle exercises each day can keep your energy up. Don't push yourself, rest when you start to feel tired and ask others for help.

Swelling of hands and feet (oedema)

You may have swelling of your hands and legs due to a build up of fluid (oedema). 

A less common side effect is swelling of the face.

High temperature (fever)

If you get a high temperature, let your healthcare team know straight away. Ask them if you can take paracetamol to help lower your temperature.

Skin changes

Skin problems include a skin rash, dry skin and itching. This usually goes back to normal when your treatment finishes. Your nurse will tell you what products you can use on your skin to help.

You might also have reddening (flushing) of the skin.

High sugar levels in the blood

You have regular blood and urine tests to check this. If you have diabetes you may need to check your blood sugar levels more often than usual. 

Numbness and tingling in fingers and toes

Numbness or tingling in fingers or toes is often temporary and can improve after you finish treatment. Tell your healthcare team if you're finding it difficult to walk or complete fiddly tasks such as doing up buttons. 

Diarrhoea or constipation

Tell your healthcare team if you have diarrhoea or constipation. They can give you medicine to help. 

Feeling or being sick

Feeling or being sick is usually well controlled with anti sickness medicines. Avoiding fatty or fried foods, eating small meals and snacks, drinking plenty of water, and relaxation techniques can all help.

It is important to take anti sickness medicines as prescribed even if you don’t feel sick. It is easier to prevent sickness rather than treat it once it has started.

Liver changes 

You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes. You have regular blood tests to check for any changes in the way your liver is working.

Less commonly your blood might show high levels of bilirubin in the blood.

You have regular blood tests to check for any changes in the levels of chemicals produced by the liver.

Headaches

Headaches can be caused by an increase in the pressure in the skull which can be life threatening. Let your doctor or nurse know straight away if you have headaches. They can give you painkillers.

Dizziness

Don’t drive or operate machinery if you feel dizzy.

Shortness of breath 

This treatment can cause lung problems. Let your doctor or nurse know straight away if you suddenly become breathless or your breathing changes.

Heart problems 

This might be a fast heart rate (tachycardia). You will have regular heart checks during and after the treatment. Tell your doctor or nurse straight away if you have any chest pain.

Less common side effects include fluid around the heart and palpitations.

Changes in mineral levels in the blood

Your blood contains different minerals and electrolytes. This treatment can change the levels of magnesium and potassium in your blood. Less commonly you might have low levels of sodium in your blood. You will have regular blood tests to check for this. 

Body pain

You might develop general pain in your body. As well as sore muscles, aching joints and bone pain. Let your team know so they can give you painkillers to help.

Hearing changes

You might have some hearing loss, especially with high pitched sounds. Tell your doctor or nurse if you notice any changes.

Eye problems and changes to eyesight

You might have eye problems such as sore, red, itchy, dry eyes (conjunctivitis) or an infection. Tell your healthcare team if you have this. They can give you eye drops or other medication to help. A less common side effect is blurred vision. Let your healthcare team know if this happens. 

Loss of appetite

You might lose your appetite for various reasons while having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks.

Mood changes

You might have some mood changes while having this treatment. Let your doctor or nurse know if you feel anxious, depressed or confused.

Difficulty sleeping

If you have difficulty sleeping, it can help to change a few things about how you try to sleep. Try to go to bed and get up at the same time each day and spend some time relaxing before you go to bed. Some light exercise each day may also help. 

Dry nose

This treatment can cause a dry nose. Talk to your healthcare team if you do have this.

Dry mouth

A dry mouth is also called xerostomia (pronounced zero-stow-mee-a). Talk to your healthcare team if you have this. They can give you artificial saliva to help with a dry mouth. It can also help to drink plenty of fluids.

Hair loss

You could lose all your hair. This includes your eyelashes, eyebrows, underarms, legs and sometimes pubic hair. Your hair will usually grow back once treatment has finished but it is likely to be softer. It may grow back a different colour or be curlier than before. 

Inflammation of the lips

Swelling (inflammation) of the lips is called cheilitis.

Tell your doctor or nurse if you have this as you may need medicine to help.

Inflammation of the pancreas

This drug can cause inflammation of the pancreas (pancreatitis). Tell your doctor straight away if you have sudden and severe pain in your tummy (abdomen).

Increased sweating

This drug might cause you to sweat more than usual. But there are ways to reduce sweating.

Let your healthcare team know if you are sweating much more than normal.

Chills

You might have chills. Let your doctor know if you have this. They may be able to prescribe medicines to help. 

Occasional side effects

These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%). You might have one or more of them. They include:

• an increased risk of getting an infection

• breathlessness and looking pale due to a low number of red blood cells that carry oxygen around your blood

• bruising, bleeding gums or nosebleeds due to a low number of platelets in your blood

• fluid around the lungs and bleeding in the lung

• weight gain

• kidney changes - you will have regular blood tests to check this

• low blood pressure

• seizures (fits)

• the herpes zoster virus (shingles) if you have had chicken pox or if you have had shingles before

• a high number of white blood cells in your blood (leucocytosis)

• a build up of a substance called ketones in the blood and urine (ketoacidosis)

• inflammation of the blood vessels

• a sudden sharp, stabbing or burning pain in the chest when you take a breath in or breathe out caused by pain in the membranes surrounding the lungs

Other side effects

There isn't enough information to work out how often these side effects might happen. You might have one or more of them. They include:

• necrotising fasciitis a rare life threatening infection of the tissue under the skin. Signs are fever, flu-like symptoms, painful cut or scratch, swelling, diarrhoea, sickness, skin blotches, blisters. Contact a doctor straight away.

• red, painful lumps under the skin usually affecting the lower legs

• blood clots that can be life threatening; signs are pain, redness and swelling where the clot is. Breathlessness can be a sign of a blood clot in the lung. Contact your advice line or doctor straight away if you have any of these symptoms.

• a rare disorder of the skin called sweet syndrome. Signs are tender plaques or nodules on the skin, fever, joint pain, eye changes and headaches. Contact the doctor if you have any of these symptoms.

• a serious reaction to an infection called sepsis. Signs include feeling very unwell, not passing urine, being sick, a very high or very low temperature, shivering. Contact your doctor straight away if you have any of these signs.

• muscles become weak, tired and painful

• ulcers around the genitals

• high levels of histamine in the body causing allergic like symptoms such as sneezing and a runny nose

• a stroke

• not enough fluid in the body (dehydration)

• a change in normal brain function caused by illness, infection, or medicines. It can cause subtle personality changes, inability to concentrate, lack of energy, abnormal movements, or loss of memory and thinking abilities.

• an increase in the level of calcium in the blood

• a heart attack

• inflammation of the heart muscle

• inflammation of the tissue around the heart

• a decrease in the blood flow to the kidneys causing them to stop working

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do you need to know?

Other medicines, food and drink

Cancer drugs can interact with medicines, herbal products, and some food and drinks. We are unable to list all the possible interactions that may happen. An example is grapefruit or grapefruit juice which can increase the side effects of certain drugs.

Tell your healthcare team about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies. Also let them know about any other medical conditions or allergies you may have.

Pregnancy and contraception

This drug may harm a baby developing in the womb. It is important not to become pregnant or get someone pregnant while you are having treatment with this drug and for at least a month afterwards.

Talk to your doctor or nurse about effective contraception before starting treatment. Let them know straight away if you or your partner become pregnant while having treatment.

Fertility

It is not known whether this treatment affects fertility in people. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Breastfeeding

Don’t breastfeed during this treatment. This is because the drugs may come through in your breast milk.

Treatment for other conditions

If you are having tests or treatment for anything else, always mention your cancer treatment. For example, if you are visiting your dentist.

Immunisation

Don’t have immunisations with live vaccines while you’re having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having. Ask your doctor or pharmacist how long you should avoid live vaccinations.

In the UK, live vaccines include rubella, mumps, measles, BCG, yellow fever and one of the shingles vaccines called Zostavax.

You can have:

• other vaccines, but they might not give you as much protection as usual
• the flu vaccine (as an injection)
• the coronavirus (COVID-19) vaccine - talk to your doctor or pharmacist about the best time to have it in relation to your cancer treatment

Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine. This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system recovers from treatment.

Contact with others who have had immunisations - You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If this happens they should keep the area covered.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray as this is a live vaccine. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn't possible, wash your hands well after changing their nappy.

More information about this treatment

For further information about each drug and the possible side effects go to the electronic Medicines Compendium (eMC) website. You can find patient information leaflets for each drug on this website.

You can report any side effect you have to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.