**1. Introduction**

Previous clinical trials confirmed that docetaxel alone displays good anticancer effects when used to treat non-small cell lung cancer. Treatment with docetaxel is associated with significant prolongation of survival [1]. Docetaxel is an antineoplastic taxoid prepared by partial chemical modification of the non-cytotoxic precursor 10-deacetyl baccatin III, which is extracted from the needles of the European pine. Its mechanism of action is to promote the polymerization and depolymerization of microtubule proteins, resulting in microtubule stabilization and microtubule hyperplasia, which prevent chromosome migration and arrest cell division in the M phase of the cell cycle [2]. Docetaxel is useful as a second-line chemotherapy for patients that are refractory to conventional platinum-based chemotherapy [3]. When combined with platinum, docetaxel displays better responses and survival rates than other platinum-containing regimens [4,5]. S-1 is a novel oral anticancer drug composed of the 5-fluorouracil (5-FU) prodrug, tegafur, and two 5-FU modulators, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate. CDHP selectively antagonizes the rate-limiting enzyme dihydropyrimidine dehydrogenase in the 5-FU degradation pathway and enhances antitumor effects by increasing blood 5-FU levels. Potassium oxonate also selectively antagonizes orotate phosphoribosyltransferase in the gastrointestinal tract after oral administration and inhibits the formation of 5-fluoronucleotides from 5-FU. In a previous phase II study, monotherapy with S-1 produced a significant response in previously treated non-small cell lung cancer [6]. Because docetaxel and S-1 have different mechanisms of action and toxicity profiles, it may be feasible and efficient to combine these drugs for the treatment of advanced non-small cell lung cancer. Previously, Yoshida et al. reported the feasibility and usefulness of this combination chemotherapy in a clinical trial for advanced gastric cancer [7].

To improve the response rate in previously-treated patients with advanced non-small cell lung cancer, we conducted a phase I/II clinical study of docetaxel plus S-1. In this regimen, docetaxel was administered on day 1 while S-1 was administered on days 1 to 14, according to the potential schedule dependency previously reported by Kano et al. [8]. The primary objectives were to determine the maximum-tolerated dose (MTD) and the recommended dose for this regimen in a phase I study and confirm its efficacy and safety in the phase II study.
