Definition
Gefitinib, which is also known as Iressa, is an anti-cancer drug used to inhibit the growth of lung cancer cells and reduce the size of a cancerous tumor.
Purpose
Gefitinib is used as a single agent for the treatment of advanced non-small cell lung cancer that has advanced or failed to respond to other kinds of treatment. It is not suitable for use as an initial treatment, but may help to shrink tumors by as much as 10% when used as a third-line therapy in patients with advanced non-small lung cancer.
Description
In May 2003, gefitinib was approved for use in the United States under the U.S. Food and Drug Administration's (FDA) accelerated approval program. Generally speaking, before the FDA approves a drug for use, a great deal of data regarding the safety, efficacy, and quality of the drug is usually compiled. In fact, it is typical for the FDA to review thousands of pages of data about a medicine under consideration for approval. One of the reasons for this is the FDA's extremely strict approval process, an approval process that is, in fact, among the strictest in the world. FDA approval means that the regulators have decided that the new drug's potential benefits outweigh its risks. When a drug is approved under the accelerated program it is done so because, as Mark B. McClellan, M.D. and FDA Commissioner states, the "FDA believes it is critical for patients to have many safe and effective treatment options available to them in their battles against disease."
In a 2004 article published in the Pfizer Journal entitled, "Enhancing Pharmaceutical Safety," Dr. Stephanie Crawford, a member of the FDA's Drug Safety and Risk Management Advisory Committee, said the following: "Approval of a drug as safe is not a blanket statement that it is without risk. It means that the risk is acceptable." Drawing on information provided by the FDA, it was further stated in the article that "the decision to approval a medicine involves consideration of the disease: a product to treat a life threatening condition may be approved even if it presents more of a certain risk, because its potential benefits are so great." In other words, the approval of a valuable cancer drug associated with an adverse side effect might be seen as more acceptable than the approval of an allergy medicine with the same side effect. As was further stated in the article, "The value of the medicine has to be seen in the context of its benefits, its known adverse effects, the severity and reversibility of these effects, and the availability of other medications for that person."
As the FDA cautiously stated in 2003, "The mechanism by which Iressa [gefitinib] exerts its clinical benefit is not fully understood. However, Iressa was developed to block growth stimulatory signals in cancer cells. These signals are mediated in part by enzymes called tyrosine kinases. Iressa blocks several of these tyrosine kinases, including the one associated with the Epidermal Growth Factor Receptor (EGFR)." Research has shown that the EGFR is sometimes found in abundance on the surface of cancer cells, causing them to divide excessively. Therefore, by blocking EGFR, it is thought that tumor growth can be thwarted.
However, gefitinib was approved by the FDA, as all drugs approved under the accelerated program, with the condition that further studies would be conducted to measure the drug's clinical benefit. According to the FDA, the drug's sponsor would be required to conduct three studies. One would evaluate gefitinib as a third-line therapy drug and evaluate if it prolonged survival as compared to the best supportive care available. Another study would compare gefitinib to docetaxel, which is another approved chemotherapy drug. And the third trial would analysis whether gefitinib is effective in reducing cancer symptoms in patients with lung cancer that are resistant to all available chemotherapy treatments. As Dr. McClellan indicated, "the studies are needed to confirm the clinical benefit, understand better which patients benefit, and evaluate long-term safety."
However, on March 4, 2005, Public Citizen in a letter to the FDA petitioned for gefitinib's removal from the market, stating that the study conducted to prove gefitinib's efficacy had failed and that the drug had already been removed from the market in Europe. Furthermore, the use of the drug has been tied to deaths in Japan. Therefore, it is possible that before long the FDA will reclassify gefitinib as an experimental drug.
Recommended Dosage
Gefitinib is available in 250 mg tablets. Dosage levels may vary, depending on the needs of the patient. However, patients generally take one 250 mg tablet a day. The tablets should not be crushed or broken and the patient should be certain to drink plenty of fluids throughout the day.
Precautions
Women who are pregnant or may become pregnant should not use gefitinib. Patients receiving gefitinib should not breast-feed their babies during the treatment cycle and for a substantial time after the treatment.
Side Effects
This drug has been associated with high toxicity in Japan. There have been reports indicating that using gefitinib caused severe side effects, such as inflammation of the lungs (interstitial pneumonia) and difficulty in breathing. Therefore, patients should report any side effects, whether they seem severe or not, to their physician. The most common side effects associated with taking 250 mg a day were:
- skin rash
- diarrhea
- acne
- dry skin
- nausea and vomiting
As reported in Applied Therapeutics: The Clinical Use of Drugs the most common side effects were skin related, which went away after the drug was discontinued. The symptoms were managed through the use of steroid creams, antihistamines, or topical or systemic antibiotics.
Key Term
- Public Citizen
- —Public Citizen defines itself as " a national, nonprofit consumer advocacy organization founded in 1971 to represent consumer interests in Congress, the executive branch and the courts."
Interactions
Gefitinib increases the effect of metoprolol and may increase the risk of bleeding in patients taking warfarin. The following drugs may decrease gefitinib's effectiveness:
- cimetidine
- phenytoin
- rifampin
- ranitidine
- sodium bicarbonate
Resources
Books
Hodgson, B. B., Kizior, R. J., Foley, M., et al. Mosby's 2005 Drug Consultant for Nurses. St. Louis, MO: Mosby, 2005.
Koda-Kimbl, M. A., Young, L. Y., Kradjan, W. A., Guglielmo, B. J., editors. Applied Therapeutics: The Clinical Use of Drugs. 10th ed. Baltimore, MD: Lippencott Williams & Wilkins, 2005.
Periodicals
Giorgianni, S. J., editor. "Enhancing pharmaceutical safety." The Pfizer Journal 8 (2004): 4–13.
Organizations
Public Citizen. 1600 20th Street, NW, Washington, DC 20009. 1-202-588-1000.
Other
Public Citizen "Cancer Drug Should Not Be Approved, Public Citizen Tells FDA." Public Citizen 1 May 2003 Public Citizen. 15 April. 2005
U.S. Food and Drug Administration "Approvals of FDA-regulated products." U.S. Food and Drug Administration Mar. 2004. U.S. Food and Drug Administration. 25 Mar. 2005
U.S. Food and Drug Administration "FDA approves new type of drug for lung cancer." U.S. Food and Drug Administration May 2003. U.S. Food and Drug Administration. 25 Mar. 2005
—Lee Ann Paradise
