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First-Line Single Agent Treatment With Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer: A Phase II Study

From the Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan

Address reprint requests to Seiji Niho, MD, Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha 6-5-1, Kashiwa, Chiba 277-8577, Japan; e-mail: siniho{at}east.ncc.go.jp

PURPOSE: We conducted a phase II study of single agent treatment with gefitinib in chemotherapy-naïve patients with advanced non–small-cell lung cancer (NSCLC) to assess its efficacy and toxicity.

PATIENTS AND METHODS: Patients received 250 mg doses of gefitinib daily. Administration of gefitinib was terminated if partial response (PR) was not achieved within 8 weeks or if tumor reduction was not observed within 4 weeks. In these cases, platinum-based doublet chemotherapy was given as a salvage treatment. We evaluated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples.

RESULTS: Forty-two patients were enrolled between March and November 2003, with 40 of these patients being eligible. The response rate was 30% (95% CI, 17% to 47%). The most common toxicity included grade 1 or 2 acne-like rash (50%) and grade 1 diarrhea (18%). Grade 2 or 3 hepatic toxicity was observed in 8% of patients. Four patients developed grade 5 interstitial lung disease (ILD). Thirty patients received second-line chemotherapy. Median survival time was 13.9 months (95% CI, 9.1 to 18.7 months), and the 1-year survival rate was 55%. Tumor samples were available in 13 patients, including four cases of PR, six cases of stable disease, and three cases of progressive disease. EGFR mutations (deletions in exon 19 or point mutations [L858R or E746V]) were detected in four tumor tissues. All four patients with EGFR mutation achieved PR with gefitinib treatment.

CONCLUSION: Single agent treatment with gefitinib is active in chemotherapy-naïve patients with advanced NSCLC, but produces unacceptably frequent ILD in the Japanese population.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

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

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