1. ¹First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan
2. ²Department of Medical Oncology, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan
3. ³Department of Respiratory Medicine, Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo 003-0804, Japan
4. ⁴Department of Respiratory Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
5. ⁵Department of Respiratory Medicine, Sapporo City General Hospital, North 11, West 13, Chuo-ku, Sapporo 060-8604, Japan
6. ⁶Department of Medical Oncology, KKR Sapporo Medical Center, 1-6 Hiragishi, Toyohira-ku, Sapporo 062-0931, Japan
7. ⁷Department of Respiratory Medicine, Asahikawa City General Hospital, 1 Kinseicho, Asahikawa 070-8610, Japan
8. ⁸Department of Respiratory Medicine, Dohoku Hospital, 7 Hanasakicho, Asahikawa 070-0901, Japan

Correspondence: K Yamazaki, E-mail: kyamazak@med.hokudai.ac.jp

Received 28 June 2006; Revised 30 August 2006; Accepted 1 September 2006.

Abstract

Retrospective analysis has shown that activating mutations in exons 18–21 of the epidermal growth factor receptor (EGFR) gene are a predictor of response to gefitinib. We conducted a phase II trial to evaluate the efficacy and safety of gefitinib as first-line therapy for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Patients with stage IIIB or IV chemotherapy-naïve NSCLC with EGFR mutation were treated with 250 mg gefitinib daily. For mutational analysis, DNA was extracted from paraffin-embedded tissues and EGFR mutations were analysed by direct sequence of PCR products. Twenty (24%) of the 82 patients analysed had EGFR mutations (deletions in or near E746-A750, n=16; L858R, n=4). Sixteen patients were enrolled and treated with gefitinib. Twelve patients had objective response and response rate was 75% (95% CI, 48–93%). After a median follow-up of 12.7 months (range, 3.1–16.8 months), 10 patients demonstrated disease progression, with median progression-free survival of 8.9 months (95% CI, 6.7–11.1 months). The median overall survival time has not yet been reached. Most of the toxicities were mild. This study showed that gefitinib is very active and well tolerated as first-line therapy for advanced NSCLC with EGFR mutations.