Gefitinib is a cancer treatment marketed under the brand name Iressa. It is not a chemotherapeutic in the traditional sense, since it does not cause the destruction of tumor cells. Instead, gefitnib interferes with the growth and spread of new cancer cells. In this respect, gefitnib is an antitumor medication rather than a cytotoxic (cell killing) drug. It is part of the class of cancer drugs known as tyrosine kinase inhibitors.

Gefitnib inhibits the phosphorylation of several tyrosine kinases inside of cells. One tyrosine kinase that gefitnib inhibits that is believed to play a role in its antitumor effect is the tyrosine kinase associated with the epidermal growth factor receptor. Epidermal growth factor receptor is a receptor that is found on both normal and cancer cells, but its presence on cancer cells is believed to explain at least some of gefitnib’s antitumor effect.

Astra Zeneca received FDA approval for gefitnib (Iressa) in May 2003. The drug’s original indication was for the treatment of advanced or malignant non-small cell lung cancer in patients that failed traditional treatment, specifically platinum and docetaxel chemotherapies. Gefitnib was approved by the FDA under accelerated approval regulations. Large clinical trials with the drug showed that it only benefitted about 10% of the patients that used the drug.

As a result, the FDA approved updated labeling and prescribing information in June 2005 that reflects a restricted approval of the drug. The current FDA approval is limited to patients that have been successfully treated or are currently treated with the drug. The approval is limited to the treatment of non-small cell lung cancer that has not responded to traditional treatment. In these patients it can be used as monotherapy, meaning the sole cancer treatment.

Theoretically, a tyrosine kinase inhibitor like gefitnib could be used in other cancers besides non-small cell lung cancer. Since it blocks the epidermal growth factor receptor tyrosine kinase, any cancer cell that expresses this protein in large amounts could be affected by the drug. The only large scale trial registered with the National Institutes of Health (NIH) to investigate the use of gefitnib in other types of cancer is one that examines the effect of the drug on recurrent glioblastoma, a type of brain tumor.

The fact that gefitnib is only effective in 10% of patients treated with the drug may be due to a particular mutation in the epidermal growth factor receptor. A group of researchers in Japan found that patients with this mutation enjoyed longer progression-free survival than those without the mutation.1 It is estimated that the 10% effect seen in large trials is approximately the percentage of patients that naturally have this mutation. Therefore, companies have developed or are developing a laboratory test to determine if a given patient has the proper mutation in this gene. A positive result on this test should predict whether gefitnib will be effective in that patient. Currently Genzyme Genetics and Biodesix offer testing for the mutation of the epidermal growth factor receptor-tyrosine kinase gene at a cost of about $1,000.

Perhaps surprisingly, the effect of gefitnib did not correlate to the amount of epidermal growth factor receptor on cancer cells. One might expect this to be the case given its proposed mechanism of action. Another drug called erlotinib (Tarceva) works by a similar mechanism as gefitnib and is approved in the same patient population. Erlotinib was approved on the basis of survival data and its effect does correlate with the amount of receptor present. In other words, patients that expressed a large amount of epidermal growth factor receptor had better results with erlotinib than those patients with lower amounts of the receptor protein.

Compared to cytotoxic anticancer drugs, gefitnib has a relatively tolerable side effect profile. Its only serious documented side effect is that it can cause damage to lungs in the form of interstitial lung disease. This occurs in about 1% of patients treated with gefitnib and the lung condition has been directly fatal in a third of patients that develop the side effect.

A tyrosine kinase inhibitor that goes after the EGFR – epidermal growth factor receptor – Gefitinib is classified as a tyrosine kinase inhibitor.

A recent Chinese study found Gefitinib was well tolerated in patients with Stage 4 non-small cell lung cancer, although the success rate was not particularly good. No drugs have good success against advanced lung cancer. An Italian study has likewise found gefitinib is more effective against NSCLC than carboplatin-paclitaxel.

Scheduling of paclitaxel and gefitinib to inhibit repopulation for optimal treatment of human cancer cells and xenografts that overexpress the epidermal growth factor receptor.

Treatment

Gefitinib, otherwise known as Iressa, is used to treat small cell lung cancer and is being studied for use against other types of cancer. (It is sometimes given for other kinds of cancer “off-label”.) It is a tyrosine kinase inhibitor and targets the epidermal growth factor receptor on the surface of some cells in the body. Gefitinib blocks these receptors from essentially telling the cell to grow and divide. It is FDA approved but it is only available to people who have already been exposed to Gefitinib. It is taken by the mouth in 250 mg tablets once a day. It works best when taken at the same time and cannot be doubled.

When taking Gefitinib you should tell your doctor if you are allergic to any medicine, additives, dyes, or foods. If you have any type of liver disease or any other medical conditions, you should let your doctor know. If you are pregnant, breast feeding, or taking any other medications or blood thinning medications, your doctor needs to be aware.

Gefitinib may interact with other drugs or supplements, causing its level to either rise or lessen in your blood. If you are taking rifampin, pherytoin, Phenobarbital, St. John’s Wort, Carbamezapine, Itraconazole, Keto Conazole, Nefazodone, Clarithromycin, cimetidine, ranitidine, metropolol, ritonavir, or other drugs for GIV or Aids, you need to let your doctor know immediately. In addition, grapefruit or grapefruit juice may also change the level of this medication in your blood. Gefitinib can also affect your body’s ability to form blood clots in order to stop bleeding, which may in turn double if you are taking any other medicine that can affect your ability to stop bleeding. Warn your doctor if you are taking aspirin, warfarin, clopidogrel, ticlopidine, or Vitamin E.

Gefitinib may cause a rash on the face and neck but will go away after the first two weeks of treatment. In some cases, the rash may be extreme and you should reduce your exposure to the sun, as it makes the rash worse. Rashes are common side effects of EGFR inhibitors. Hives and swelling are less common side effects.

Muscle weakness and soreness are possible side effects, as are mouth sores. This drug may cause diarrhea and can lead to chemical imbalances in your body. You may want to be prescribed medication to help against this. It may also increase liver enzyme levels in your blood, so you will likely have to do blood tests. You may also develop lung disease and changes in your vision. Let your doctor know if you experience shortness of breath, coughing, or eye irritation. It is possible to develop severe lung disease. Food shouldn’t affect the medication. Be sure to ask your doctor for more information.

Gefitinib has proven cancer-fighting ability, even though it works better for some people than others. Even though it has side effects such as the thinning of blood, diarrhea, and rashes, oncologists often feel the benefits outweigh the downsides.

A recent Chinese study found Gefitinib was well tolerated in patients with Stage 4 non-small cell lung cancer, although the success rate was not particularly good. No drugs have good success against advanced lung cancer. An Italian study has likewise found gefitinib is more effective against NSCLC than carboplatin-paclitaxel.