Iressa (gefitinib)

Iressa is an anticancer drug that inhibits an enzyme (tyrosine kinase) present in lung cancer cells, as well as other cancers and normal tissues, that appears to be important to the growth of cancer cells. It is taken alone, not with other chemotherapy.

The recommended daily dose of Iressa is one 250 mg tablet with or without food. Higher doses do not give a better response and causes increased toxicity.

FDA approval of Iressa was based on a phase III trial. The multicenter clinical trial in the U.S. evaluated the tumor response rate of Iressa 250 and 500 mg/day in 216 subjects with advanced non-small cell lung cancer whose disease had progressed after at least two prior chemotherapy regimens including a platinum drug and docetaxel. Iressa was taken once daily at approximately the same time each day. Subjects received Iressa, 102 (47%) and 114 (53%) receiving 250 mg and 500 mg daily doses, respectively. In addition, 41% of the subjects had received two prior treatment regimens, 33% three prior treatment regimens, and 25% four or more prior treatment regimens.

Results showed that the overall response rate for the 250 and 500 mg doses combined was 10.6% (95% CI: 6%, 16.8%). Response rates appeared to be highly variable in subgroups of the treated population: 5.1% (4/79) in males, 17.5% (11/63) in females, 4.6% (5/108) in previous or current smokers, 29.4% (10/34) in nonsmokers, 12.4% (12/97) with adenocarcinoma histology, and 6.7% (3/45) with other NSCLC histologies. Similar differences in response were seen in a multinational study in subjects who had received 1 or 2 prior chemotherapy regimens, at least l of which was platinum-based. In responders, the median time from diagnosis to study randomization was 16.7 months (range 8 to 34 months).

Adverse events associated with the use of Iressa may include (but are not limited to) the following:

• Diarrhea
• Rash
• Acne
• Dry Skin
• Nausea
• Vomiting
• Pruritus
• Anorexia
• Asthenia

Gefitinib is an EGFR tyrosine kinase inhibitor. It works by binding to the intracellular enzyme (tyrosine kinase) of the EGFR to directly block signals turned on by triggers outside or inside the cell.

The activity of epidermal growth factor and its receptor, the EGFR, have been identified as key drivers in the process of cell growth and replication. Heightened activity at the EGF receptor, whether caused by an increase in the concentration of ligand around the cell, an increase in receptor numbers or a decrease in receptor turnover or receptor mutation, can lead to an increase in the drive for the cell to replicate. There is now a body of evidence to show that the EGFR-mediated drive is increased in a wide variety of solid tumours, including non-small cell lung cancer, prostate cancer, breast cancer, gastric cancer, colon cancer, ovarian cancer and tumours of the head and neck.

Gefitinib is an anilinoquinazoline with the chemical name 4-Quinazolinamine. The mechanism of the clinical antitumor action of gefitinib is not fully characterized. Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells. No clinical studies have been performed that demonstrate a correlation between EGFR receptor expression and response to gefitinib.

De Marinis F, Nelli F, D'Auria G. EGFR inhibitors: clinical results. Suppl Tumori. 2002 Nov-Dec;1(6):S5-6. Review.

Fujiwara K, Kiura K, Ueoka H, Tabata M, Hamasaki S, Tanimoto M. Dramatic effect of ZD1839 ('Iressa') in a patient with advanced non-small-cell lung cancer and poor performance status. Lung Cancer. 2003 Apr; 40(1):73-6.

Schultz J.Apparent adverse drug reactions prompt concern about Iressa. J Natl Cancer Inst. 2003 Apr 16;95(8):577-9.

Tsuruo T. Molecular cancer therapeutics: recent progress and targets in drug resistance. Intern Med. 2003 Mar; 42(3):237-43.

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