Clinical development of S-1 for non-small cell lung cancer: a Japanese perspective

Abstract

For more than a decade, S-1 has been investigated aggressively against non-small cell lung cancer (NSCLC) in Japan. Recently, two randomized phase III trials of S-1 combined with cisplatin (CDDP) or carboplatin (CBDCA) compared with the standard platinum doublet chemotherapy were reported. S-1 and CDDP was noninferior to CDDP and DTX in terms of overall survival (OS) (median survival time [MST] 16.1 versus 17.1 months, respectively; hazard ratio [HR] 1.013; 96.4% confidence interval [CI] 0.837-1.227). Noninferiority of S-1 and CBDCA compared with CBDCA and paclitaxel was also confirmed for OS (MST 15.2 versus 13.3 months, respectively; HR 0.928; 99.2% CI 0.671-1.283). The noninferiority design employed an upper CI limit of HR<1.322 in the former trial and HR<1.33 in the latter. S-1 combined with CDDP or CBDCA was thought to be one of the standard platinum doublet regimens in the first-line setting for patients with advanced NSCLC in Japan. Some additional interesting phase I and II studies have been published in Japan. They include studies of S-1 as first-line chemotherapy when combined with nonplatinum agents; as second-line chemotherapy; within chemoradiotherapy for locally advanced disease; and in the postoperative adjuvant setting. This review will also describe the use of S-1 for the treatment of NSCLC in these settings.

Keywords: S-1; clinical trial; non-small cell lung cancer.

Figure 1.

Unique metabolism of S-1. S-1 (FT, CDHP, Oxo) is an oral ‘DPD inhibitory fluoropyrimidine’ (DIF). 5-FU, fluorouracil; CDHP, 5-chloro-2,4-dihydroxypyridine; DPD, dihydropyrimidine dehydrogenase; GI, gastrointestinal; OPRT, orotate phosphoribosyltransferase; Oxo, potassium oxonate.