Phase II randomized study of daily gefitinib treatment alone or with vinorelbine every 2 weeks in patients with adenocarcinoma of the lung who failed at least 2 regimens of chemotherapy

BACKGROUND. The objective of this study was to assess the efficacy of adding chronic, intermittent, low-dose vinorelbine to gefitinib treatment for patients who had adenocarcinoma of the lung who failed ≥2 regimens of chemotherapy. METHODS. Patients were randomized into 2 arms: Oral gefitinib 250 mg daily (the G arm) or vinorelbine 15 mg/m² as an intravenous infusion on Day 1 and oral gefitinib 250 mg daily on Days 2 through 14 every 2 weeks (the GV arm). From August 2004 to October 2005, 48 patients were enrolled. Epidermal growth factor receptor (EGFR) exon 18 through 21 nucleotide sequence analysis and fluorescence in situ hybridization were performed in patients who had tumor tissue specimens available for analysis. RESULTS. After randomization, each arm had 24 patients. However, 3 patients refused vinorelbine treatment and were given gefitinib treatment only. Thus, 27 patients received G treatment, and 21 patients received GV treatment. Objective response rates were 55.6% in the G arm and 52.4% in the GV arm. All toxicities in both arms were mild. The 1-year progression-free survival rate was 57.1% in the GV arm and 21.2% in the G arm (P =.008). The median survival was 13.3 months in the G arm and 23.4 months in the GV arm (P =.1231). Three of 6 patients (50%) had an exon 19 in-frame deletion, and 2 of 10 patients had EGFR gene high polysomy or amplification (20%). CONCLUSIONS. Gefitinib was highly effective in ethnic Chinese patients with adenocarcinoma of the lung who failed previous platinum and taxane treatment. The addition of low-dose vinorelbine every 2 weeks produced a significantly better 1-year progression-free survival rate.