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File:Gefitinib structure.svg
Systematic (IUPAC) name
Clinical data
Routes of
Legal status
Legal status
  • S4 (Au), POM (UK), ℞-only (U.S.)
Pharmacokinetic data
Bioavailability 59% (oral)
Protein binding 90%
Metabolism Hepatic (mainly CYP3A4)
Biological half-life 6–49 hours
Excretion Faecal
CAS Number 184475-35-2
ATC code L01XE02 (WHO)
PubChem CID 123631
DrugBank APRD00997
Chemical data
Formula C22H24ClFN4O3
Molar mass 446.902 g/mol[[Script error: No such module "String".]]
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Gefitinib (INN) (pronounced /ɡɛˈfɪtɨnɪb/) (Iressa) is a drug used in the treatment of certain types of cancer. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts a growth factor in cancer cells. It is marketed by AstraZeneca and Teva.

Mechanism of action

Gefitinib is the first selective inhibitor of epidermal growth factor receptor's (EGFR) tyrosine kinase domain. Thus gefitinib is an EGFR inhibitor. The target protein (EGFR) is also sometimes referred to as Her1 or ErbB-1 depending on the literature source.

EGFR is overexpressed in the cells of certain types of human carcinomas - for example in lung and breast cancers. This leads to inappropriate activation of the anti-apoptotic Ras signalling cascade, eventually leading to uncontrolled cell proliferation. Research on gefitinib-sensitive non-small cell lung cancers has shown that a mutation in the EGFR tyrosine kinase domain is responsible for activating anti-apoptotic pathways.[1][2] These mutations tend to confer increased sensitivity to tyrosine kinase inhibitors such as gefitinib and erlotinib. Of the types of non-small cell lung cancer histologies, adenocarcinoma is the type that most often harbors these mutations. These mutations are more commonly seen in Asians, women, and non-smokers (who also tend to more often have adenocarcinoma).

Gefitinib inhibits EGFR tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited, and malignant cells are inhibited.[3]

Clinical uses

Gefitinib is currently marketed in over 64 countries. In Europe gefitinib is indicated since 2009 in advanced NSCLC in all lines of treatment for patients harbouring EGFR mutations. This label was granted after gefitinib demonstrated as a first line treatment to significantly improve progression-free survival vs. a platinum doublet regime in patients harbouring such mutations. IPASS has been the first of four phase III trials to have confirmed gefitinib superiority in this patient population. In most of the other countries where gefitinib is currently marketed it is approved for patients with advanced NSCLC who had received at least one previous chemotherapy regime. However, applications to expand its label as a first line treatment in patients harbouring EGFR mutations is currently in process based on the latest scientific evidence.

While gefitinib has yet to be proven to be effective in other cancers, there is potential for its use in the treatment of other cancers where EGFR overexpression is involved.

Erlotinib is another EGFR tyrosine kinase inhibitor that has a similar mechanism of action than gefitinib. However, since there is so far little evidence of erlotinib as a first line treatmetn in NSCLC, its label is currently restricted to patients who have at least received one previous chemotherapy regime.


IPASS (IRESSA Pan-Asia Study) was a randomized, large-scale, double-blinded study which compared gefitinib vs. carboplatin/ paclitaxel as a first line treatment in NSCLC.[4] IPASS studied 1,217 patients with confirmed adenocarnicoma histology which were former or never smokers. A pre-planned sub-group analyses showed that PFS was significantly longer for IRESSA than chemotherapy in patients with EGFR mutation positive tumours (HR 0.48, 95 per cent CI 0.36 to 0.64, p less than 0.0001), and significantly longer for chemotherapy than IRESSA in patients with EGFR mutation negative tumours (HR 2.85, 95 per cent CI 2.05 to 3.98, p less than 0.0001). This is the first time a targeted monotherapy has demonstrated significantly longer PFS than doublet chemotherapy.

Genzyme test

On September 26 2005, Genzyme Corp. announced that it would market a test to detect EGFR mutations, designed to help predict which lung cancer patients may respond best to some therapies, including gefitinib and erlotinib. This method is used to identify ahead of time which patients may respond to medications in this drug class.[5] The test, expected to cost about $975, examines the genetics of tumors removed for biopsy for mutations that make them susceptible to treatment.

The EGFR mutation test may also help Genentech and AstraZeneca win regulatory approval for use of their drugs as initial therapies. Currently the TK inhibitors are approved for use only after other drugs fail. In the case of gefitinib, the drug works only in about 10% of patients with advanced non-small cell lung cancer, the most common type of lung cancer. This led the Food and Drug Administration in June 2009 to partially withdraw the drug in the U.S., no longer allowing its prescription for new patients.[6] The drug remains on the market in Europe. --

Adverse effects

As gefitinib is a selective chemotherapeutic agent, its tolerability profile is far superior to previous cytotoxic agents. Adverse drug reactions (ADRs) do still occur however, but may be preferable to the fatal consequences of not taking the therapy.

Acne is reported very commonly. Other common adverse effects (≥1% of patients) include: diarrhoea, nausea, vomiting, anorexia, stomatitis, dehydration, skin reactions, paronychia, asymptomatic elevations of liver enzymes, asthenia, conjunctivitis, blepharitis.[7]

Infrequent adverse effects (0.1–1% of patients) include: interstitial lung disease, corneal erosion, aberrant eyelash and hair growth.[7]

See also


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  3. Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
  4. Mok TS et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Eng J Med 2009; 361. 10.1056/NEJMoa0810699.
  6. FDA Safety Alert
  7. 7.0 7.1 Rossi S, editor. Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook; 2004. ISBN 0-9578521-4-2.