Dinutuximab (Intravenous)

Dinutuximab is classed as a GD2-binding monoclonal antibody, it is administered by injection and is combined with other medications to treat children who have a form of cancer known as high-risk neuroblastoma.

Overview

Also known by its brand names Unituxin, Dinutuximab is classed as a GD2-binding monoclonal antibody and it is used to treat high-risk neuroblastoma - a form of cancer that is mostly found in young children. It is used in conjunction with the medicines granulocyte-macrophage-colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA) in patients who have attained a small response to previous initial multi-medicine, multimodality therapy.

Dinutuximab acts by binding to the glycolipid GD2. Glycolipid GD2 is a molecule that is manifested in neuroblastoma tumours. It has an extremely restricted expression on normal tissues, such as those in the central nervous system, sympathetic nervous system or peripheral nerves. Once it has bound itself to the cell surface GD2, Dinutuximab induces the dissolution of these cells (cell lysis) through the ADCC (antibody-dependent cell-mediated cytotoxicity) and CDC (complement-dependent cytotoxicity). Consequently, cell lysis occurs as the reaction of a specific lysin disrupting the cell membrane which then damages and destroys the GD2 cell.

Neuroblastoma is one of the more common solid tumours known to affect children. It can happen anywhere in the body, but it is a tumour that occurs in the sympathetic nervous system (SNS) and is mostly found in the adrenal glands or the abdomen, In rarer cases, a neuroblastoma may be found in nerve tissue alongside the spinal cord in areas by the neck, chest, abdomen or pelvis. The causes of this form of cancer are unknown and it has an average of a 67% survival rate. However, this survival rate is higher in younger patients. Infants who have been diagnosed before reaching one year old have a five-year survival rate of 83%.

Following effective treatment alongside other medications, dinutuximab can offer children with a positive outlook and increased the chance of recovery. It is administered by injection and must only be prescribed and administered by a doctor or healthcare professional.

Conditions treated

  • Pediatric high-risk neuroblastoma

Type of medicine

  • GD2-binding monoclonal antibody

Side effects

Dinutuximab has the potential to cause unwanted and serious side effects. For this reason, it is essential that patients or carers keep track of any reactions that you or your child may be experiencing. Serious reactions are extremely rare, however, in most cases, they will require emergency medical treatment and must be alerted to a healthcare professional immediately.

A common reaction to dinutuximab is diarrhea. Usually, this does not require medical treatment and it should go away once your body has become adjusted to the medicine. However, if you find that it worries you or remains persistent, make sure to discuss it with a doctor.

This medicine can also cause a large drop in blood pressure causing patients to feel dizzy or lightheaded. This is more likely to occur when you initially start taking this medicine and might stop following continued use. If you or your child faints, it is important that you discontinue its use until you have spoken with your doctor. Following your treatment, make sure to stand or sit up slowly if you are feeling dizzy.

There are a number of more common side effects that patients may experience when taking this medication. These may be unpleasant and should be brought to the attention of your doctor when possible.

More common side effects include:

  • Bleeding gums
  • Blurred vision
  • Chills
  • Cloudy urine
  • Coma
  • Confusion
  • Convulsions
  • Decrease or increase in the amount of urine
  • Difficult or labored breathing
  • Dry mouth
  • Fast or irregular heartbeat
  • Headache
  • Increased thirst
  • Irregular heartbeat
  • Loss of appetite
  • Lower back or side pain
  • Muscle pain or cramps
  • Nausea or vomiting
  • Noisy breathing
  • Numbness or tingling in the hands, feet, or lips
  • Painful or difficult urination
  • Pale skin
  • Redness of the skin
  • Sore throat
  • Sweating
  • Ulcers, sores, or white spots in the mouth
  • Unusual tiredness or weakness

Dinutuximab also has the potential to cause a rare but severe type of allergic reaction known as an infusion reaction. This is incredibly harmful and can be life-threatening. Because of this, it will need emergency medical intervention. If you or your child experience a cough, any trouble breathing, hives, itching or a skin rash, lightheadedness, dizziness, fainting, a tightness in the chest or swelling of the face or lips, contact a doctor immediately.

Make sure to check with a healthcare professional right away if you or your child are experiencing burning, numbness, tingling, or painful feelings in the arms, hands, legs, or feet. These are indicators of a serious condition called peripheral neuropathy.

Tell your doctor straight away if you or your child have a cloudy urine, an unusual amount of urine, lightheadedness, fainting sickness, stomach pain, or swelling of the hands, ankles, or feet after receiving this medicine. These may be indicators of a rare and serious condition known as capillary leak syndrome.

Additionally, dinutuximab can cause a severe condition called hemolytic uremic syndrome. This will require immediate medical attention and can be incredibly unpleasant.

Contact a medical professional right away if you or your child has any of the following symptoms:

  • Black, tarry, stools
  • Blood in the urine or stools
  • Fever

Increased or decreased urination

  • Pinpoint red spots on the skin
  • Stomach pain
  • Swelling of the face, hands, ankles, feet, or lower legs
  • Unusual bleeding or bruising
  • Unusual weakness
  • Yellow eyes or skin

This is not a full list of side effects that patients may experience whilst taking this medication. If you become concerned about any symptoms that you or your child may be having, make sure to discuss them with your doctor.

Dosage

The dose that you will be given of dinutuximab will be dependent on a number of factors including your illness, age and your current state of health. The advised dose of dinutuximab in all patients is 17.5 mg administered as an IV infusion over a period of 10 to 20 hours for four days in a row. This should be repeated at a maximum of five cycles. Alternately, an advised dose of 0.875 mg/m2/h infused for an initial 30 minutes is recommended. This infusion rate can be slowly increased as tolerated, but should never exceed 1.75 mg/m2/h.

Infusions should be initiated following four hours of preparation and they should not be administered as an IV push or bolus.

Interactions

No drug interaction studies have been performed with dinutuximab. For this reason, it is important that your doctor is aware of any medical conditions, allergies or sensitivities that you may have before you begin treatment. You must also let them know of any other prescription or over-the-counter medications that you may be taking. Considering diet and lifestyle factors is also advised, as alcohol, tobacco and certain foods may have negative interactions or increase any side effects.

Warnings

As there are some potentially serious and harmful side effects that can occur when taking dinutuximab, it is important that you notify your doctor of any symptoms and reactions that you may be experiencing. They will also want to keep a close track on your progress, with regular appointments and check-ups to ensure that your treatment is as effective as possible.

This medicine can cause a temporary decrease in the number of white blood cells and platelets in your blood. This increases the possibility of getting an infection and, as platelets are essential for proper blood clotting, it can cause excessive bleeding. If you do have a decreased number of platelets or white blood cells, it is important to take certain precautions to reduce your risk of infection or bleeding. Make sure to avoid people with infections and check with your doctor as soon as possible if you suspect that your or your child think you are getting one. You should also alert your doctor urgently if you experience any abnormal bleeding and bruising, bloody, black or tarry stools, blood when urinating or small red spots on your skin. Alongside this, you should be cautious when you use a toothbrush, dental floss, or any other dental hygiene tools. Your healthcare professional may recommend alternative ways of oral hygiene that pose a lower risk. No dental work should take place without the consent of your doctor. It is also important that you do not cut yourself when using sharp objects and that you avoid any contact sports or situations which could result in injury. Finally, to avoid infection, never touch the inside of your nose or your eyes without washing your hands first.

Dinutuximab can have very harmful effects on unborn babies. For this reason, pregnancy is not recommended and should be avoided. It is essential to use an effective form of birth control during your treatment and for at least two months following your last dose. The effects of this medication and breastfeeding are unclear, however, due to its harmful effects on fetuses it is unrecommended and poses a risk. If you think you may be pregnant, are planning on having children or are breastfeeding, make sure to discuss it with your doctor before your treatment begins.

Storage

As this medication will only ever be administered and handled by your doctor or trained medical professionals, it is unlikely that you will ever come into contact with it. It should be stored in a medical refrigerator at a temperature of 2°C to 8°C until the time of its use.

Summary

Mostly used in pediatric patients to treat a type of cancer known as high-risk neuroblastoma, effective treatment of dinutuximab can prolong the life of cancer patients and contribute to a full recovery. It works by binding itself to cancerous cells and destroys them by damaging their membrane.

Dinutuximab is just one medicine in a treatment regime to combat types of cancer, being administered alongside granulocyte-macrophage-colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA). It is given to patients who have already received some form of response to previous first-line multi-medicine, multi-modality therapy.

There is a risk of potentially harmful and unpleasant side effects when taking this medication and it also has the potential to lower white blood cells and platelets. For this reason, it is vital that patients and carers alter their lifestyle to ensure the best treatment and least risk of adverse reactions, they must also closely monitor any side effects that they may be experiencing. For patients who experience a decline in white blood cells or platelets, they are at a higher risk of bleeding and infection. This makes it necessary to be extra careful around any situations that may result in injury or infection, such as when using nail clippers, brushing teeth and being on public transport or around people who may have infections. This also means that this treatment will have a large impact on a person's life, stopping them from doing tasks and activities that they may have been able to do before. However, the long-term benefits of taking dinutuximab far outweigh the benefits. Successful treatment can mean your child or you living a longer life and potentially cancer-free life.

Patients should also be prepared for regular blood tests and visits to the doctor. Your doctor will want to monitor you closely whilst you are undergoing treatment, as this will ensure that they can track its progress and decide on whether you or your child should continue or alter treatment.