Phase I study of S-1 plus paclitaxel combination therapy as a first-line treatment in elderly patients with advanced non-small cell lung cancer.

This phase I study was aimed at determining the maximum tolerated dose (MTD) and recommended dose (RD) for oral S-1 plus paclitaxel combination therapy in elderly patients with non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients (age, >70 years) with stage III/IV NSCLC were treated with paclitaxel intravenously at four dose levels (DLs), 60, 70, 80, and 90 mg/m2, on day 1 and 8, and with S-1 (80 mg/m2) orally on days 1-14 every 3 weeks. MTD was defined as the dose at which two of the initial three patients experienced dose-limiting toxicities (DLTs). Three patients were added when the initial three patients experienced DLTs. The dose administered in three of the six patients with DLTs met the definition of MTD. The RD was defined as a dose 1 DL below the MTD. Fifteen patients including six on DL 1 and three each on DLs 2, 3, and 4 were enrolled. One patient experienced a DLT (febrile neutropenia) at DL 1. The remaining DLTs were noted at DL 4 (in one patient each): febrile neutropenia, grade (G) 3 skin rash, G3 diarrhea, G3 stomatitis, and G3 international normalized ratio (INR) elevation. The MTD of paclitaxel was 90 mg/m2. The RD for both S-1 and paclitaxel was 80 mg/m2 (DL 3). The response rate was 45.5% (8 of 15 patients achieved a partial response). In conclusion, the RD of both S-1 and paclitaxel was 80 mg/m2 in the combination therapy for chemotherapy-naïve patients with advanced NSCLC.