Iressa

The Food and Drug Administration today announced the approval of Iressa (gefitinib). Iressa is a new 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. Iressa is used as a single agent for the treatment of non-small cell lung cancer (NSCLC) that has progressed after, or failed to respond to two other types of chemotherapy (drugs used to kill cancer cells). see Iressa.com or FDA page

FDA/Center for Drug Evaluation and Research
Created: May 5, 2003

How it is given

Iressa is taken as a tablet once a day.

How it works

Iressa works by blocking (inhibiting) signals within the cancer cells, which prevents a series of chemical reactions that cause the cell to grow and divide. It is known as a signal transduction inhibitor. This process is described in detail below.

On the surface of many types of cancer cell are structures known as epidermal growth factor receptors (EGFRs). The receptors allow epidermal growth factor (a particular protein present in the body) to attach to them. When the epidermal growth factor (EGF) attaches to the receptor, it causes a chemical called tyrosine kinase to trigger chemical processes inside the cell to make it grow and divide.

Iressa attaches itself to the EGF receptor inside the cell, which blocks the activation of tyrosine kinase, and switches off the signals from the EGFR. It therefore has the potential to stop the cancer cells from growing. It works in a different way to both chemotherapy and hormonal therapy.

FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets.

Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. Oncologist. 2003;8(4):303-6.

Division of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland 20857, USA. cohenma@cder.fda.gov

On May 5, 2003, gefitinib (Iressa), ZD1839) 250-mg tablets received accelerated approval by the U.S. Food and Drug Administration as monotherapy treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes efficacy and safety results of relevant clinical trials. Effectiveness was demonstrated in a randomized, double-blind, phase II, multicenter trial comparing two oral doses of gefitinib (250 mg/day versus 500 mg/day). Two hundred sixteen patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving gefitinib 250 mg/day and in 8% (6 of 76) of patients receiving gefitinib 500 mg/day. The overall objective response rate for both doses combined was 10.6% (15 of 142 patients) (95% confidence interval 6.0%-16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range 4.6-18.6+ months). Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV NSCLC patients. Patients were randomized to receive gefitinib (250 mg or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n = 1,093) or carboplatin plus paclitaxel (n = 1,037). Results from those studies showed no benefit (response rate, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Most toxicities were Common Toxicity Criteria grade 1 or 2. Interstitial lung disease (ILD) has been observed in patients receiving gefitinib. Worldwide, the incidence of ILD is about 1% (2% in the Japanese postmarketing experience and about 0.3% in a U.S. expanded access program). Approximately one-third of the cases were fatal. Physicians should promptly evaluate new or worsening pulmonary symptoms. If ILD is confirmed, appropriate management includes discontinuation of gefitinib. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point response rate. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or greater survival. Accelerated approval regulations require the sponsor to conduct further studies to verify that gefitinib therapy produces such a benefit.