This information is about cetuximab, which is a drug used to treat people with cancer of the bowel (colon and rectum) and people with cancer of the head and neck. Cetuximab may also be used to treat other types of cancer as part of a research trial.

What is cetuximab?

Cetuximab is a type of drug known as a monoclonal antibody. It is not a chemotherapy drug. It is a targeted ‘magic bullet’ type biological therapy. In the UK it is currently used to treat cancer of the bowel / rectum that has come back after initial treatment and has spread to other parts of the body (advanced or metastatic cancer). In bowel cancer treatment, cetuximab is usually given in combination with the drug irinotecan and fluorouracil, but sometimes given with oxaliplatin. Cetuximab is also used with radiotherapy to treat locally advanced head and neck cancer.

Although cetuximab is licensed and can be prescribed in the UK, it has not been approved for use by the National Institute for Health and Clinical Excellence (NICE). NICE gives advice on which new drugs or treatments should be available on the NHS. As a result, cetuximab may not be widely available on the NHS. Normally the only way to receive it on the NHS is if you are in a clinical trial, or if your local health authority has given special permission – known as an ETA (exceptional treatment arrangement) – This involves a lengthy application process and can be a bit of a lottery.

UPDATE – It may soon be available on NHS for 16 weeks in patients with liver metastases that are currently inoperable – ask for details

Cetuximab is also being used in research trials to treat other types of cancer, including lung cancer (NSCLC) and breast cancer. You may also be offered it as part of an early trial for other types of cancer.

Cetuximab is mainly given alongside chemotherapy, or with radiotherapy. It can also be given on its own after chemotherapy has finished as ‘continuation’ or ‘maintenance’ therapy.

Monoclonal antibodies

Monoclonal antibodies are used to try to destroy some types of cancer cells while causing little harm to normal cells. They are designed to recognise certain proteins (receptors) that are found on the surface of particular cancer cells.

One type of receptor is known as epidermal growth factor receptors or EGFRs. When growth factors, such as epidermal growth factor, bind to the receptor, the cancer cell is stimulated to grow, divide and spread.

How cetuximab works

Cetuximab attaches itself to the EGFRs and prevents the receptors from being activated. This stops the cells from dividing. It therefore has the potential to stop the cancer cells from growing.

Cetuximab may also make the cancer cells more sensitive to chemotherapy and radiotherapy.

Tests may be done to find whether a gene called k-Ras in the tumour cells is normal or mutated before cetuximab is given. This can help the doctors to know whether you are likely to benefit from this treatment. Testing can be done on samples of the cancer cells at the same time as diagnosis of the cancer, or by using cells from previous biopsies or surgery.

Patients with a mutated K-Ras gene DO NOT respond to Cetuximab or Panitumumab and it will not be given. Patients with a ‘normal’ – wild type – K-Ras gene have a good chance of responding to Cetuximab or Panitumumab.

What it looks like

Cetuximab is a colourless liquid.

How it is given

Cetuximab is given by a drip into the vein (intravenously) through a fine tube (cannula) inserted into a vein. The first dose is given slowly, usually over two hours. After this, doses are given weekly and this normally takes about an hour. The first dose is usually larger than the weekly maintenance treatments. You may be given other medicines before cetuximab to lessen the side effects during treatment.

Possible side effects

Each person’s reaction to a cancer drug is different. Some people have very few side effects, while others may experience more. If you notice any effects which you think may be due to the drug, but which are not listed here, please discuss them with your doctor.

The side effects of cetuximab are generally mild and some of these can be reduced with medicines. Cetuximab is given with the chemotherapy drug irinotecan, so many of the side effects you might have will be caused by the irinotecan. Cetuximab does not increase the side effects of irinotecan.

Allergic reactions

Occurs rarely, 5 – 10% of the time. Signs of a reaction include skin rashes and itching, a feeling of swelling in the tongue or throat, irritation of the nasal passages, wheezing, a cough and breathlessness. You will be monitored closely during your treatment, but tell your nurse or doctor if you have any of these symptoms. To reduce the chance of developing an allergic reaction, certain drugs (antihistamines) can be given before the infusion. The drip can also be slowed down or stopped until the reaction is over.

Skin changes

Mild skin rashes are very common and occur in most patients. Often it is no more than dry skin and a blotchy pimply rash. They begin during the first two weeks of treatment and usually go away completely when the treatment ends.

Some people have more severe skin changes, which can include reddening of the skin, and red pimples and spots (like acne) on the face. The skin of the face may become flaky and scaly. Some people have dry skin or eczema on their fingertips, elbows and extremities, which is sore and itchy. If you have any of these skin changes, let your doctor know straight away. If you have very severe skin problems the length of time between treatments may be extended or the dose may be lowered. The rash can sometimes be itchy. Use moisurising creams like E45 or aqueous cream. If the rash worsens your doctor may prescribe steroid or antibiotic creams or tablets. You can also get dry skin and split nails.

Treatment can be prescribed by your doctor to reduce the rash, such as steroid and antibiotic creams. To help reduce the reddening, it is best to avoid foods that make the skin go red, such as chillies and alcohol.

To help reduce dry skin eczema, it is helpful to avoid things that make your skin dry, such as too much central heating and soap. Your doctor can prescribe creams to moisturise your skin.

Breathlessness

Rare. Some people may become breathless. This is more likely if you have an existing lung problem. Let your doctor know if you notice any increase in breathlessness.

Feeling sick (nausea) and less commonly being sick (vomiting)

Rare. Your doctor can prescribe very effective anti-sickness (antiemetic) drugs to prevent or greatly reduce nausea.

Diarrhoea

This can usually be controlled with medicine such as imodium (loperamide), but tell your doctor if it is severe or if it continues. 5 – 10% of patients having cetuximab can experience a severe diarrhoea. It is important to drink plenty of fluids if you have diarrhoea.

Fever and chills

If you develop a fever or chills let your doctor know.

Sore eyes

You may notice that your eyes become sore, red and itchy. This is known as conjunctivitis and your doctor can prescribe eye drops to help.

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ADDITIONAL INFORMATION FOR HEALTHCARE PROFESSIONALS

ADVERSE REACTIONS SIGNIFICANT

Except where noted, percentages reported for cetuximab monotherapy.

>10%:

• Central nervous system: Fatigue (89%), pain (17% to 51%), headache (26% to 33%), insomnia (10% to 30%), fever (27% to 30%), confusion (15%), anxiety (14%), chills/rigors (13%), depression (7% to 13%)
• Dermatologic: Acneform rash (76% to 90%; grades 3/4: 1% to 17%), rash (89%), dry skin (49%), pruritus (11% to 40%), nail changes/disorder (16% to 21%)
• Endocrine & metabolic: Hypomagnesemia (55%; grades 3/4: 6% to 17%)
• Gastrointestinal: Abdominal pain (26% to 59%), constipation (26% to 46%), diarrhea (25% to 39%), vomiting (25% to 37%), nausea (mild-to-moderate 29%), weight loss (7% to 27%), anorexia (23%), stomatitis (10% to 25%), xerostomia (11%)
• Neuromuscular & skeletal: Weakness (45% to 48%), bone pain (15%)
• Respiratory: Dyspnea (17% to 48%), cough (11% to 29%)
• Miscellaneous: Infection (13% to 35%), infusion reaction (15% to 21%; grades 3/4: 2% to 5%; 90% with first infusion)

1% to 10%:

• Cardiovascular: Peripheral edema (10%), cardiopulmonary arrest (2%; with radiation therapy)
• Dermatologic: Alopecia (4%), skin disorder (4%)
• Endocrine & metabolic: Dehydration (2% to 10%)
• Gastrointestinal: Dyspepsia (6%)
• Hematologic: Anemia (9%)
• Hepatic: Alkaline phosphatase increased (5% to 10%), transaminases increased (5% to 10%)
• Neuromuscular & skeletal: Back pain (10%)
• Ocular: Conjunctivitis (7%)
• Renal: Renal failure (1%)
• Respiratory: Pulmonary embolus (1%)
• Miscellaneous: Sepsis (1% to 4%)

>1% (Limited to important or life-threatening):

• Abscess formation, arrhythmia, blepharitis, bronchospasm, cardiac arrest, cellulitis, cheilitis, hoarseness, hypertrichosis, hypotension, interstitial lung disease (occurred between the fourth and eleventh doses), leukopenia, loss of consciousness, MI, paronychial inflammation, sepsis, skin fissure, stridor
• Dermatologic toxicity: Acneform rash has been reported in 76% to 88% of patients (severe in 1% to 17%), usually developing within the first 2 weeks of therapy; may require dose modification. Acneform rash should be treated with topical and/or oral antibiotics; topical corticosteroids are not recommended. Other dermatologic toxicities, including dry skin, fissures, hypertrichosis, paronychial inflammation, and skin infections have been reported. Sunlight may exacerbate skin reactions.
• Infusion reactions: [U.S. Boxed Warning]: Severe infusion reactions (bronchospasm, stridor, hoarseness, urticaria, hypotension, loss of consciousness, cardiac arrest) have been reported in 2% to 5% of patients (~90% with the first infusion despite the use of prophylactic antihistamines).Note: Although a 20 mg test dose was used in some studies, it did not reliably predict the risk of an infusion reaction, and is not recommended. In case of severe reaction, treatment should be stopped and permanently discontinued. Immediate treatment for anaphylactic/anaphylactoid reactions should be available during administration. Patients should be monitored for at least 1 hour following completion of infusion, or longer if a reaction occurs. Mild-to-moderate infusion reactions (chills, fever, dyspnea) are managed by slowing the infusion rate (by 50%) and administering antihistamines.
• Interstitial lung disease (ILD): Has been reported; use with caution in patients with pre-existing lung disease. Permanently discontinue with confirmed ILD.

Concurrent drug therapy issues:

• Combination with cisplatin and radiation therapy: Safety and efficacy have not been established when used in combination with radiation therapy and cisplatin.

MECHANISM OF ACTION

Recombinant human/mouse chimeric monoclonal antibody which binds specifically to the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1) and competitively inhibits the binding of epidermal growth factor (EGF) and other ligands. Binding to the EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased matrix metalloproteinase and vascular endothelial growth factor production.

PHARMACODYNAMICS / KINETICS

• Distribution: Vd: ~2-3 L/m2
• Half-life elimination: ~112 hours (range: 63-230 hours)