Gefitinib (Iressa)

General information

Class/mechanism: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Activating mutations of EGFR can drive tumor growth by activating pathways that promote proliferation, invasion, angiogenesis, metastasis, and inhibition of cell death. Gefitinib binds to the EGFR tyrosine kinase domain and inhibits these over-active signalling pathways. There are differences between specific EGFR mutations and their likelihood of clinical response to EGFR TKIs.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

• Non-small cell lung cancer

Patient drug information

• Gefitinib (Iressa) package insert
• Gefitinib (Iressa) patient drug information (Chemocare)
• Gefitinib (Iressa) patient drug information (UpToDate)

History of changes in FDA indication

• 5/5/2003: Granted accelerated FDA approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies. (Based on IDEAL2)
• 6/17/2005: Due to the negative confirmatory trial, access of this drug was restricted to patients currently receiving and benefiting from Iressa; patients who have previously received and benefited from Iressa; and previously enrolled patients or new patients in non-Investigational New Drug (IND) clinical trials approved by an IRB prior to June 17, 2005. (Based on ISEL)
• 7/13/2015: FDA approved for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. (Based on IFUM and IPASS)

Resistance and sensitivity mechanisms

1. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. Epub 2004 Apr 29. link to original article PubMed
2. Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005 Feb 24;352(8):786-92. link to original article PubMed

Also known as

• Code name: ZD1839
• Brand names: Cangib, Denrit, Geffy, Gefitec, Gefitero, Gefonib, Geftib, Geftican, Gefticip, Geftilon, Geftinat, Geftiwel, Iressa, KabiGef