[Development of novel molecular targeted drug, "Iressa", for the treatment of malignant diseases--its basic and...

One year has passed since the launch of a new molecular targeted agent, Iressa (generic name: Gefitinib), in Japan ahead of other countries in the world. Gefitinib is the first selective Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor. Gefitinib was investigated clinically by a single dose ascending study and 3-day multiple dosing study in male volunteers in the UK initially. On confirmation of tolerability by those studies, 4 Phase I studies were conducted in patients with solid tumours generally known to over-express EGFR, with a result of 250 mg or 500 mg (oral administration) decided to be chosen as the recommended dose for Phase II studies. A Phase II study was then conducted in 9 countries including European countries, Australia, and Japan, using once daily oral dosing regimen. In this study gefitinib demonstrated response rate of 18.4% (19/103), and disease control rate of 54.4% (56/103) in advanced non-small cell lung cancer patients (with 1 or 2 previous chemotherapy regimens) at a dose level of 250 mg/day. Symptom improvement rate, which was determined using lung cancer sub-scale (LCS) for QOL assessment, was 40.3% (27/67), and median time to symptom improvement was 8 days (on the initial assessment). In 3 months after the launch, 39 lung injury deaths of patients were reported including deaths attributed to interstitial pneumonia, which was covered broadly by mass media. It is, however, considered that development of Iressa, the first EGFR tyrosine kinase inhibitor showing effects on solid tumours, for clinical use through assiduous researches on molecular targeted agents has truly great significance. This paper gives an overview covering development history to date, clinical study results, and post-launch safety reports.