On May 5, 2003, the FDA approved gefitinib (Iressa®, a trademark of AstraZeneca) for treatment of advanced non-small cell lung cancer (NSCLC), the most common form of lung cancer in the United States. Gefitinib is intended for patients whose cancer has progressed despite treatment with other chemotherapy drugs.

Specifically, the FDA approved gefitinib 250 milligram (mg) tablets as monotherapy treatment for patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies. Gefitinib is not recommended for use in combination with chemotherapy.

Gefitinib was evaluated in a multicenter United States clinical trial in patients with advanced non-small cell lung cancer. Patients were entered in the trial after their disease had progressed or they’d experienced intolerable toxicity associated with at least two prior chemotherapy regimens, including both a platinum-based drug and the drug docetaxel.

One hundred forty-two evaluable patients (that is, those with disease that cannot be measured directly by the size of the tumor but can be evaluated by other methods) received gefitinib at a dose of either 250 milligrams a day (mg/day) or 500 mg/day. Approximately 75 percent had adenocarcinoma histology (alone or mixed with squamous cell histology).

Partial tumor responses occurred in 15 of 142 evaluable patients for a response rate of 10.6 percent (95CI: 6-16.8 percent) overall. Responses occurred in 9 of 66 patients receiving 250 mg/day (13.6 percent) and in 6 of 76 patients receiving 500 mg/day (7.8 percent). Median duration of response was 7.0 months (range 4.6 -18.6+ months).

Two large controlled randomized trials in the first-line treatment of NSCLC showed no benefit from adding gefitinib to doublet, platinum-based chemotherapy.

In the patients who received Iressa monotherapy for treatment of NSCLC, the most common adverse drug reactions reported were diarrhea (sometimes associated with dehydration), rash, acne, dry skin, nausea, vomiting, and pruritis (a severe itching reaction). These events generally occurred within the first month of therapy and usually were mild to moderate.

Cases of interstitial lung disease (ILD) have been observed in patients receiving gefitinib at an overall incidence of about 1 percent, and approximately one-third of the cases have been fatal. (The reported incidence of ILD was about 2 percent in the Japanese post-marketing experience, about 0.3 percent in approximately 23,000 patients treated with gefitinib in a U.S. expanded access program, and about 1 percent in the studies of first-line use in NSCLC [but with similar rates in both treatment and placebo groups]).

In the event of acute onset or worsening of pulmonary symptoms (dyspnea, cough, fever), gefitinib therapy should be interrupted and a prompt investigation of these symptoms should occur. If interstitial lung disease is confirmed, gefitinib should be discontinued and the patient treated appropriately.

The approved dose for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies is one 250 mg tablet once a day with or without food. Higher doses do not give a better response and cause increased toxicity.

This indication is approved on the basis of objective response rate under accelerated approval provisions. Randomized controlled clinical trials will be performed to evaluate whether gefitinib treatment is associated with clinical benefit, such as improved survival or symptom improvement. Gefitinib received fast-track designation and priority review.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

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