Background: S-1 is an oral anticancer agent containing a mixture of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, which has been shown to have a radiosensitizing effect in preclinical models. Recent phase II studies have shown that chemoradiotherapy using cisplatin and S-1 yields promising progression-free survival (PFS) durations of 15 to 20 months in non-elderly (less than 75 years old) patients (pts) with locally advanced NSCLC. We conducted a phase I study of CBDCA, S-1 and TRT for elderly pts with locally advanced NSCLC. Methods: The eligibility criteria included pts with unresectable stage III NSCLC, a chemotherapy-naïve status, PS 0 to 1, and age ≥ 71 years. Pts received CBDCA (AUC 3-5) on day 1 and S-1 (30-40mg/m2 twice daily) on days 1 to 14, q4w, up to 4 cycles, plus concurrent TRT at a total dose of 60Gy. The initial dose of CBDCA was AUC 3 and that of S-1 was 60mg/m2/day. Three to 6 pts were entered at each dose level. Results: In all, 18 pts were enrolled between August 2011 and May 2015 from 4 hospitals in Japan. The patient characteristics were as follows: median age, 77 years (71-83 years); male/female ratio, 16/2; PS 0, 11 pts; tumor histopathological type: adenocarcinoma in 7 pts, squamous cell carcinoma in 7 pts, and NSCLC- NOS in 4 pts. All 4 cycles of CBDCA plus S-1 could be completed in 9 pts (50%), and the median number of cycles was 3.5 (range, 1 to 4). TRT at 60 Gy was completed in all 18 pts (100%). At dose level 4 (CBDCA 4 and S-1 40mg/m2 twice daily), 2/3 pts showed dose-limiting toxicities (DLTs), including G4 thrombocytopenia, G3 esophagitis and febrile neutropenia, and at dose level 3 (CBDCA 3 and S-1 40mg/m2 twice daily), 2/6 pts showed DLTs, including G3 pneumonitis and fatigue. PR was achieved in 12 pts, and the overall response rate was 67%. The median PFS was 15.3 months (95% confidence interval, 13.1 to 17.6 months), with a median follow-up period of 12.3 months in censored cases. Conclusions: The recommended doses of CBDCA and S-1 for a phase II study were determined to be AUC 3 and 40mg/m2 twice daily, respectively. A phase II study of this treatment is underway. Clinical trial information: UMIN000005794.