Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations.
OBJECTIVE
This study was undertaken to investigate the efficacy and the feasibility of gefitinib for chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.


METHODS
The EGFR gene status in various tumor samples obtained from chemotherapy-naïve advanced NSCLC patients was examined by DNA sequencing of EGFR exons 18 to 23. Patients harboring EGFR mutations received gefitinib (250 mg/d) alone. The response rate, progression-free survival (PFS), and toxicity profile were assessed prospectively.


RESULTS
Between June 2004 and October 2005, 75 patients were examined for the EGFR status, and 25 patients (33%) harbored EGFR mutations. EGFR mutations were significantly frequent in females (P < .01) and never or light smokers (P < .001). Sixteen patients with EGFR mutations were enrolled onto the study. The overall response rate in these patients was 75% (95% CI, 54% to 96%), and the disease control rate was 88% (95% CI, 71% to 100%). The median PFS time of these patients was 9.7 months (95% CI, 7.4 to 9.9 months). No life-threatening toxicity was observed.


CONCLUSIONS
Treatment with gefitinib alone for chemotherapy-naïve NSCLC patients with EGFR mutations could achieve a high efficacy with acceptable toxicity. To assess the proper timing of gefitinib in such patients, a subsequent randomized trial comparing gefitinib with standard chemotherapy is warranted.
Inoue
Akira
A
Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, 4-1, Seiryomachi, Aoba-ku, Sendai 980-8575, Japan. akinoue@idac.tohoku.ac.jp
Suzuki
Takuji
T
Fukuhara
Tatsuro
T
Maemondo
Makoto
M
Kimura
Yuichiro
Y
Morikawa
Naoto
N
Watanabe
Hiroshi
H
Saijo
Yasuo
Y
Nukiwa
Toshihiro
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001120:Arginine; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005240:Feasibility Studies; D005260:Female; D000077156:Gefitinib; D018698:Glutamic Acid; D006801:Humans; D007930:Leucine; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D018698:Glutamic Acid; D001120:Arginine; D066246:ErbB Receptors; D007930:Leucine; D000409:Alanine; D000077156:Gefitinib