Phase I/II trial of gemcitabine plus oral TS-1 in elderly patients with advanced non-small cell lung cancer: Thoracic oncology research group study 0502

A phase I/II trial of TS-1 combined with gemcitabine was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients older than 70 years of age received TS-1 orally b.i.d. on days 1-14 and gemcitabine intravenously on days 8 and 15 every 4 weeks. In phase I (n = 22), each cohort received escalating doses of TS-1 (30-40 mg/m2 b.i.d.) and gemcitabine (800-1000 mg/m2); MTD was 40 mg/m2 b.i.d. TS-1 and 1000 mg/m2 gemcitabine; RD was 30 mg/m2 b.i.d. TS-1 and 1000 mg/m2 gemcitabine. Dose-limiting toxicities included a grade 3 infection, skin toxicity, and stomatitis. In phase II (n = 37), the overall response rate was 27% (90% confidence interval (CI): 15-42%) and the median time to progression and overall survival were 4.2 months (90% CI: 3.2-5.7) and 12.9 months (90% CI: 10.4-14.7), respectively. The most common grade 3 or higher toxicity was neutropenia (45.9%), and thrombocytopenia was observed in 13.5% of patients. Two cases each of grade 3 pneumonitis and skin toxicity were observed, but nonhematological toxicities occurred at generally low frequencies. TS-1 with gemcitabine is a promising doublet regimen in elderly patients with advanced NSCLC with acceptable toxicities.