Panitumumab (ABX-EGF)

This information is about panitumumab which is one of a group of cancer drugs, known as monoclonal antibodies. This drug is being used as a treatment for people with advanced cancer (cancer that has spread to other parts of the body), particularly advanced cancer of the bowel and rectum. Panitumumab is currently mainly being used as part of clinical trials. Developing a new drug When a drug is being developed it has to go through various stages of research, called clinical trials or studies. These are intended to establish a safe dosage, to discover what side effects the drug may have and to find out which cancers it may be used to treat. The trials also find out how effective the drug is, whether it is better than the existing treatments, or has extra benefit when given with these treatments. At this stage, Panitumumab is only available only to a small number of people in the UK, usually in clinical trials (e.g. PICCOLO). In certain circumstances it may also be given to individual patients who have been selected by their doctor as suitable (this is called a named-patient basis). Monoclonal antibodies Monoclonal antibodies can destroy some types of cancer cells, while causing little harm to normal cells. They recognise certain proteins or receptors that are found on the surface of some types of cancer cells. The monoclonal antibody recognises the protein or receptor and 'locks' on to it (like a key in a lock). There are different types of antibodies that work in different ways. Once the monoclonal antibody has attached to the protein or receptor it can: * · Trigger the body’s immune system to attack the cancer cell and cause the cell to be destroyed. * * · Block a receptor from connecting with a different protein that helps the cell to grow. This may stop the cells from growing and dividing, or prevent cancer cells from developing a new blood supply. How panitumumab works Panitumumab belongs to a subgroup of monoclonal antibodies, known as epidermal growth factor receptor (EGFR) inhibitors. It is not a chemotherapy drug. It is a targeted ‘magic bullet’ type biological therapy. Epidermal growth factor (EGF) is a protein that is present in the body. There are receptors for EGF on the surface of many types of cancer cell. When EGF binds to these receptors, chemical signals are triggered which cause the cells to grow and reproduce. Panitumumab attaches itself to the EGF receptor, and prevents it from being activated. This stops the internal chemical signals, and inhibits the growth of cancer cells that have the EGFR on their surface. It works in a different way from chemotherapy. 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 Panitumumab is a clear liquid. How it is given Panitumumab is given through a small tube (cannula) inserted into a vein. It may be given in combination with chemotherapy drugs, or alone. Panitumumab is given as a drip (infusion) over one hour, usually once every three weeks. Possible side effects Each person's reaction to cancer treatment is unique. Some people have very few side effects, while others may experience more. The side effects described in this information will not affect everyone who is given panitumumab. The drug may be used in combination with chemotherapy, so people will also have side effects from the chemotherapy. The side effects mentioned below are those caused by panitumumab. We have outlined the most common side effects, but have not included those that are very rare and therefore extremely unlikely to affect you. As panitumumab is a new treatment, we do not know all the possible side effects it may cause. If you notice any effects that you think might be due to the drug, but that are not listed in this information, please discuss them with your doctor or nurse. Skin rash This is the most common side effect of the drug and it affects most people. It occurs after 2–3 weeks of treatment, usually in the form of a rash, rather like acne, which appears on the face and the upper part of the body. It often gradually fades over the following weeks, even if your treatment with panitumumab continues. 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. Less common side effects Infusion Reactions These are very rare with Panitumumab because the antibody has been artificially engineered to be ‘human’, so your immune system should not react to it, like it sometimes does with Cetuximab. It is easily treatable if it occurs. Diarrhoea This can usually be easily controlled with medicine (loperamide or codeine), but let your doctor know if it is severe or continues. 5 - 10% of patients can get a severe diarrhoea. It is important to drink plenty of fluids if you have diarrhoea. Tiredness and a general feeling of weakness It is important to allow yourself plenty of time to rest. Feeling sick (nausea) and being sick (vomiting) There are very effective anti-sickness drugs to prevent, or greatly reduce, nausea. If you experience this, it may begin a few hours after the treatment is given, and can last for up to a few days. If the sickness is not controlled, or continues, tell your doctor, who can prescribe other anti-sickness drugs which may be more effective. ADDITIONAL INFORMATION FOR HEALTHCARE PROFESSIONALS ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Peripheral edema (12%) Central nervous system: Fatigue (26%) Dermatologic: Skin toxicity (90%; grades 3/4: 16%), erythema (65%; grades 3/4: 5%), acneiform rash (57%; grades 3/4: 7%), pruritus (57%; grades 3/4: 2%), exfoliation (25%; grades 3/4: 2%), paronychia (25%), rash (22%; grades 3/4: 1%), fissures (20%; grades 3/4: 1%), acne (13%; grades 3/4: 1%) Endocrine & metabolic: Hypomagnesemia (38%; grades 3/4: 4%) Gastrointestinal: Abdominal pain (25%), nausea (23%), diarrhea (21%; grades 3/4: 2%), constipation (21%), vomiting (19%) Respiratory: Cough (14%) 1% to 10%: Dermatologic: Dry skin (10%), nail disorder (other than paronychia: 9%) Gastrointestinal: Stomatitis (7%), mucositis (6%) Ocular: Eyelash growth (6%), conjunctivitis (4%), ocular hyperemia (3%), lacrimation increased (2%), eye/eye lid irritation (1%) Miscellaneous: Antibody formation (=5%), infusion reactions (3%; grades 3/4: 1%) <1% (Limited to important or life-threatening): Allergic reaction, anaphylactoid reaction, chills, dyspnea, fever, hypocalcemia, hypoxia, pulmonary embolism, pulmonary fibrosis, pulmonary infiltrate * Dermatologic toxicity: [U.S. Boxed Warning]: Dermatologic toxicities have been reported in ~90% of patients (severe in 12% of patients); may include dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin and skin fissures. Severe skin toxicities may be complicated by infection, sepsis, or abscesses. The median time to development of skin (or ocular) toxicity was 2 weeks, with resolution ~7 weeks after discontinuation. Withhold treatment (and monitor) for severe or life-threatening dermatologic toxicities; may require dose reduction or permanent discontinuation. Patients should minimize sunlight exposure; may exacerbate skin reactions. Gastric mucosal, ocular and nail toxicities have also been reported. * * Diarrhoea: May cause diarrhea; the incidence and severity of chemotherapy-induced diarrhea is increased with combination chemotherapy. Due to the potential for severe diarrhea and other toxicities, use with combination chemotherapy regimens is not recommended. * Electrolyte depletion: May occur during treatment and after treatment is discontinued; monitor for hypomagnesemia and hypocalcemia. * * Infusion reactions: [U.S. Boxed Warning]: Severe infusion reactions (anaphylactic reaction, bronchospasm, fever, chills, and hypotension) have been reported in ~1% of patients. Discontinue infusion for severe reactions; permanently discontinue in patients with persistent severe infusion reactions. Appropriate medical support for the management of infusion reactions should be readily available. Mild to moderate infusion reactions are managed by slowing the infusion rate. * * Pulmonary fibrosis: Has been reported (rarely); permanently discontinue treatment if interstitial lung disease, pneumonitis or lung infiltrates develop. Use caution with lung disease; patients with underlying lung disease were excluded from clinical trials. MECHANISM OF ACTION Recombinant human IgG2 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 intracellular tyrosine kinases, resulting in inhibition of cell survival, growth, proliferation and transformation. PHARMACODYNAMICS / KINETICS Half-life elimination: ~7.5 days (range: 4-11 days)