A phase II randomized trial of gefitinib alone or with tegafur/uracil treatment in patients with pulmonary adenocarcinoma who had failed previous chemotherapy.

Background: Tegafur/uracil (UFT) is suitable for metronomic chemotherapy because of its underlying antiangiogenesis mechanism. This study aimed to assess the efficacy of adding daily oral UFT to gefitinib treatment in patients with pulmonary adenocarcinoma who had failed previous chemotherapy.

Methods: Taiwanese patients who had adenocarcinoma of the lung and failed previous chemotherapy were randomized into gefitinib 250 mg daily alone (G) or plus daily oral UFT (GU). From November 2005 to August 2009, 115 patients were enrolled.

Results: There were 58 patients in the G arm and 57 in the GU arm. One-year progression-free survival (PFS) was 18% in the G arm and 36.7% in the GU arm (p = 0.03). Fifty-four patients had tissue samples available for tumor epidermal growth factor receptor (EGFR) sequence analysis: 16 classical mutations and 8 wild types in the G arm, and 20 classical mutations and 10 wild-types in the GU arm. The addition of UFT significantly improved PFS in patients with EGFR mutations (14.4 versus 7.6 months, p = 0.0061). Forty-three patients underwent tumor tissue microvessel density measurement, and a trend favoring the addition of UFT to gefitinib treatment was found in those with low microvessel density (median PFS: 11.8 versus 2.8 months, p = 0.0536). The median survival time was 18.3 months in the G arm and 23.6 months in the GU arm (p = 0.381).

Conclusion: Gefitinib plus UFT treatment had better PFS than gefitinib alone treatment. Gefitinib is effective in patients with EGFR mutations, and the addition of UFT treatment produced better PFS in these patients with mutations.