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Originally published as JCO Early Release 10.1200/JCO.2005.05.4692 on June 19 2006

Journal of Clinical Oncology, Vol 24, No 21 (July 20), 2006: pp. 3340-3346
© 2006 American Society of Clinical Oncology.
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Prospective Phase II Study of Gefitinib for Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer With Epidermal Growth Factor Receptor Gene Mutations

Akira Inoue, Takuji Suzuki, Tatsuro Fukuhara, Makoto Maemondo, Yuichiro Kimura, Naoto Morikawa, Hiroshi Watanabe, Yasuo Saijo, Toshihiro Nukiwa

From the Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University; and Department of Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

Address reprint requests to Akira Inoue, MD, Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, 4-1, Seiryomachi, Aoba-ku, Sendai 980-8575, Japan; e-mail: akinoue{at}idac.tohoku.ac.jp

PURPOSE: 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.

PATIENTS AND 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.

CONCLUSION: 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.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


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