[Gefitinib and epidermal growth factor receptor gene mutation].
Epidermal growth factor receptor (EGFR) gene mutations are frequent in lung cancer of Asian ethnicity, female gender, non-smokers,and of adenocarcinoma histology. About 80% of the patients with EGFR mutations respond to EGFR tyrosine kinase inhibitor (TKI) including gefitinib and erlotinib, while only 10% of those without EGFR mutations do so. Therefore, EGFR mutation is being recognized as one of the most reliable predictive factors in gefitinib treatment. Another important issue in clinical practice is fatal interstitial lung disease (ILD) in patients with gefitinib treatment, especially for Asian patients. A nested case-control study recently conducted in Japan identified some risk factors which cause ILD. About half of the acquired resistance to gefitinib that almost always occurs during the course of gefitinib administration is reportedly caused by secondary mutation at codon 79 0 (T 79 0 M). EGFR-TKIs are not universally effective for lung cancer,but these drugs are effective in patients who have particular characteristics. Therefore, patients who would benefit from gefitinib therapy should be included in clinical trials. Based on this concept, phaseIII clinical trials comparing gefitinib monotherapy with standard platinum-based chemotherapy in lung cancer patients with EGFR mutations are ongoing.
Dept. of Thoracic Surgery, Aichi Cancer Center Hospital, Japan.
Takayuki
T
Fukui
Tetsuya
T
Mitsudomi
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy; D012907:Smoking
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib