This information is about erlotinib, which is commonly known as Tarceva®. It can be used to treat people with advanced non-small cell lung cancer (NSCLC). Erlotinib may also be used to treat other types of cancer such as pancreatic cancer.

Trials are in progress to find out if Tarceva is best given alone or in combination with chemotherapy or radiotherapy.

What is Tarceva?

Tarceva belongs to a group of cancer drugs known as epidermal growth factor receptor (EGFR) inhibitors. It is a type of drug called a tyrosine kinase inhibitor. It can be used to treat people with non-small cell lung cancer (NSCLC), whose cancer has come back after, or not responded to, at least one course of chemotherapy. It is also increasingly used in pancreatic cancer, either alone, or with Gemcitabine.

Epidermal growth factor receptor inhibitors

Epidermal growth factor receptor inhibitors are used to try to destroy some types of cancer cells while causing little harm to normal cells.

Structures called epidermal growth factor receptors (EGFRs) sit on the surface of many types of cancer cells. Epidermal growth factor is a protein present in the body. The receptors allow epidermal growth factor to attach to them. When these growth factors bind to the receptors, a protein called tyrosine kinase (TK) triggers chemical signals to make the cell grow and divide.

Tarceva attaches itself to the tyrosine kinase protein and prevents the chemical signals from being produced. This may stop the cell dividing. Tarceva therefore may be able to stop the cancer cells from growing. It works in a different way from chemotherapy. It is a ‘magic bullet’ type targeted biological therapy.

What Tarceva looks like

Tarceva is a tablet.

How it is given

It is taken as a single dose each morning (usually 150mg) with a large glass of water, at least one hour before (or two hours after) a meal.

Possible side effects

Each person’s reaction to an anti-cancer drug is different. Some people have very few side effects, while others may experience more. If you do 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 Tarceva are generally mild and some of these can be reduced with medicines. As it is still a new drug, it is too early to know everything about the possible side effects.

A rash

Many people develop a rash, particularly on their face, neck, chest, back and arms. This generally starts about 8–10 days after starting treatment but usually improves after a few weeks. In most people the rash is mild. However, it is important to let your doctor know if you develop a rash. Sometimes the rash can be itchy. You can use moisurising creams such as E45 or aqueous cream. If the rash gets very severe your doctor might prescribe steroid or antibiotic creams, or even tablets.

Diarrhoea

This is also quite common but, again, it is usually mild and can be controlled easily with medicine (imodium – loperamide). Tell your doctor if it is severe or if it continues. It is important to drink plenty of fluids if you have diarrhoea. Let your doctor know if you develop any black ‘tarry’ looking stools.

Tiredness (fatigue) and a general feeling of weakness

Fatigue is a less common side effect but is not often severe. It is important to allow yourself plenty of time to rest.

Feeling sick (nausea) and being sick (vomiting)

It is quite common to feel sick but this is usually very easy to control. Some people will actually be sick. Your doctor can prescribe very effective antisickness (anti-emetic) drugs to prevent or greatly reduce nausea. If the sickness is not controlled, or if it continues, tell your doctor. They can prescribe other anti-sickness drugs which may be more effective.

Eye problems

Tarceva can occasionally affect the cornea of the eye (the clear part at the front of the eye), but this is rarely severe. It is recommended that people taking this drug have an assessment of the cornea before and during treatment to detect any early signs of corneal problems.

Sore mouth

Rarely Tarceva can cause a sore mouth. Your mouth may become sore, or you may notice small ulcers during this treatment. Drinking plenty of fluids and cleaning your teeth regularly can help. Tell your nurse or doctor if you have any of these problems, as special mouthwashes and medicines to prevent or clear any mouth infection can be prescribed.

Liver Problems

Tarceva can cause liver problems in patients who have poor liver function to start with, so frequent blood tests will be done initially to check for this. If you have impaired liver function you may need a lower dose of Tarceva, or you may not be able to have it at all.

Additional information

Some other medicines can be harmful to take when you are having tarceva. Let your doctor know about any medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.

Contraception

It is not advisable to become pregnant or father a child while taking tarceva, as the developing foetus may be harmed. It is important to use effective contraception while taking this drug, and for at least a few months afterwards. It is important to discuss this with your doctor.

Smoking may make tarceva work less effectively.

Things to remember about Tarceva tablets

• Keep the tablets in a safe place where children cannot reach them, as tarceva could harm them.
• Store them in their original container.
• If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist. Do not flush them down the toilet or throw them away.
• If you are sick just after taking the tablets let your doctor know, as you may need to take another dose. Do not take another tablet without first telling your doctor.
• If you forget to take a tablet, do not take a double dose. Tell your doctor and keep to your regular dose schedule.

ADDITIONAL INFORMATION FOR HEALTHCARE PROFESSIONALS

ADVERSE REACTIONS SIGNIFICANT

Adverse reactions reported with monotherapy:

>10%:

• Central nervous system: Fatigue (52% to 79%)
• Dermatologic: Rash (75% to 76%; grade 3: 8%; grade 4: <1%; median onset: 8 days), pruritus (13%), dry skin (12%)
• Gastrointestinal: Diarrhea (54% to 55%; grade 3: 6%; grade 4: <1%; median onset: 12 days), anorexia (52% to 69%), nausea (33% to 40%), vomiting (23% to 25%), stomatitis (17% to 19%), abdominal pain (11%)
• Ocular: Conjunctivitis (12%), keratoconjunctivitis sicca (12%)
• Respiratory: Dyspnea (41%), cough (33%)
• Miscellaneous: Infection (24% to 34%)

1% to 10%:

• Hepatic: ALT increased (grade 2: 4%)
• Respiratory: Pneumonitis/pulmonary infiltrate (3%), pulmonary fibrosis (3%)

Significant adverse reactions reported with combination (erlotinib plus gemcitabine) therapy:

• Cardiovascular: Deep venous thrombosis (4%), cerebrovascular accident (2%; including cerebral hemorrhage), MI/myocardial ischemia (2%), arrhythmia, syncope
• Central nervous system: Fever (36%), depression (19%), headache (15%)
• Dermatologic: Rash (69%)
• Gastrointestinal: Diarrhea (48%), weight loss (39%), stomatitis (22%), ileus, pancreatitis
• Hematologic: Hemolytic anemia, microangiopathic hemolytic anemia with thrombocytopenia (1%)
• Hepatic: ALT increased (grade 2: 31%, grade 3: 13%, grade 4: <1%), AST increased (grade 2: 24%, grade 3: 10%, grade 4 <1%), hyperbilirubinemia (grade 2: 17%, grade 3: 10%, grade 4: <1%)
• Renal: Renal insufficiency
• Respiratory: Dyspnea (24%), cough (16%), ILD-like events (3%)
• Miscellaneous: Infection (39%)

Mono- or combination therapy: <1% (Limited to important or life-threatening):

Acute renal failure, bronchiolitis, corneal ulcerations, episcleritis, epistaxis, gastritis, gastroduodenal ulcers, gastrointestinal bleeding, gastrointestinal hemorrhage, hair/nail disorders (alopecia, brittle/loose nails, eyelash/brow changes, hirsutism, paronychia), hearing loss, hematemesis, hematochezia, hepatic failure, hepatorenal syndrome, hepatotoxicity, interstitial lung disease, melena, peptic ulcer bleeding, pulmonary fibrosis, pulmonary infiltrates, rash (acneiform; sparing prior radiation field), tympanic membrane perforation

MECHANISM OF ACTION

The mechanism of erlotinib’s antitumor action is not fully characterized. The drug is known to inhibit overall epidermal growth factor receptor (HER1/EGFR)- tyrosine kinase. Active competitive inhibition of adenosine triphosphate inhibits downstream signal transduction of ligand dependent HER1/EGFR activation.

PHARMACODYNAMICS / KINETICS

• Absorption: Oral: 60% on an empty stomach; almost 100% on a full stomach
• Distribution: 94-232 L
• Protein binding: 92% to 95% to albumin and alpha1-acid glycoprotein
• Metabolism: Hepatic, via CYP3A4 (major), CYP1A1 (minor), CYP1A2 (minor), and CYP1C (minor)
• Bioavailability: Almost 100% when given with food; 60% without food
• Half-life elimination: 24-36 hours
• Time to peak, plasma: 1-7 hours
• Excretion: Primarily as metabolites: FAeces (83%; 1% as unchanged drug); urine (8%)