UFT Plus Vinorelbine in Advanced Non-small Cell Lung Cancer: A Phase I and an Elderly Patient-Directed Phase II Study

The combination of tegafur-uracil (UFT) with vinorelbine has provided synergistic activity against non-small cell lung cancer (NSCLC) in experimental models. The recommended dose of UFT in combination with vinorelbine in NSCLC was determined in a phase I study. The phase II study evaluated efficacy and tolerability of this combination in elderly patients. Vinorelbine was infused on days 1 and 8, and UFT was administered twice daily on days 2 to 6 and days 9 to 13 of a 3-week cycle. UFT and vinorelbine were increased during the phase I study from 400 to 600 mg/d and 20 to 25 mg/m2, respectively, in 12 patients. In the phase II portion, previously untreated elderly patients were treated with 600 mg/d UFT and 20 mg/m2 vinorelbine. At the dose level of 600 mg/d UFT and 25 mg/m2 vinorelbine, dose-limiting toxicity of neutropenia or neutropenic fever was observed in two of three patients, determining the recommended dose of 600 mg/d UFT and 20 mg/m2 vinorelbine. In 30 evaluable elderly patients of the phase II study, the response rate was 27% (8/30). The median survival and progression-free survival time was 11.8 (range 2.7–34.8) and 5.0 (range 0.5–32.5) months, respectively. Grade 3 or grade 4 neutropenia and grade 3 anemia occurred in 40% and 7% of phase II patients, respectively. Gastrointestinal toxicity was frequent but mild. As the most serious toxicity, pneumonitis was observed in three patients. This combination of UFT and vinorelbine is both feasible and active in the treatment of elderly patients with advanced NSCLC.