Gefitinib for the treatment of non-small-cell lung cancer.
Gefitinib is an orally bioavailable, EGF receptor tyrosine kinase inhibitor and was the first targeted drug to be approved for non-small-cell lung cancer (NSCLC). Identification of objective tumor regressions with gefitinib in NSCLC patients has resulted in intense, worldwide clinical and basic research directed toward finding the optimal use of gefitinib in NSCLC. A recent large international Phase III study (IRESSA NSCLC Trial Evaluating Response and Survival Against Taxotere [INTEREST]) comparing gefitinib and docetaxel in unselected pretreated patients showed equivalent survival with better tolerability and quality of life. In addition, a Phase III study (WJTOG0203) evaluating gefitinib as sequential therapy after platinum-doublet chemotherapy showed the improved progression-free survival time. Furthermore, a large-scale randomized study (IRESSA Pan-Asia study [IPASS]) comparing gefitinib monotherapy with carboplatin/paclitaxel for previously untreated patients with adenocarcinoma who were never- or light-smokers showed an improved progression-free survival time in the gefitinib arm. A smaller Phase III study of pretreated Japanese patients (V-15-32) also demonstrated no difference in overall survival compared with docetaxel, with a statistically greater overall response rate. Somatic mutations in the EGFR gene, the target of gefitinib, were associated with dramatic and durable regressions in patients with NSCLC. Currently, investigators are trying to determine the optimal approach to select patients for treatment with gefitinib. This article aims to briefly summarize the profile of gefitinib, EGFR mutations, landmark trials with gefitinib and, also, ongoing trials that may herald an era of individualized therapy in at least some NSCLC patients.
Hida
Toyoaki
T
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Kanokoden, Chikusa-ku, Nagoya, Japan. 107974@aichi-cc.jp
Ogawa
Shizu
S
Park
Jang Chul
JC
Park
Ji Young
JY
Shimizu
Junichi
J
Horio
Yoshitsugu
Y
Yoshida
Kimihide
K
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011799:Quinazolines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib