Gefitinib (
Iressa) is a novel targeted
therapy that inhibits the
tyrosine kinase activity of the
epidermal growth factor receptor by competitively blocking the
ATP binding site. In preclinical studies
gefitinib has shown potent activity in a number of
tumor models, including several
lung cancer cell lines and xenografts. Two large randomized Phase II studies (
IDEAL 1 and IDEAL 2) in pretreated
non-small cell lung cancer reported a response rate approaching 20% in second-line patients and approximately 10% in those pretreated with two or more
chemotherapy regimens. The median survival in these two studies approached 6-8 months. As a first-line
therapy,
gefitinib has been assessed in combination with two different
chemotherapy regimens in two large randomized studies (INTACT 1 and INTACT 2). Both studies failed to show an improvement in survival on a total patient accrual of >1000 patients in each study. Other end points (e.g., time to progression and response rate) were also not improved by the addition of
gefitinib. Additional studies are indicated to assess the possible role of
gefitinib in the maintenance of patients who received
chemotherapy or
chemoradiotherapy. Studies investigating
gefitinib as first-line monotherapy are also required.