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.

A randomized, phase 2 study of deoxyuridine triphosphatase inhibitor, TAS-114, in combination with S-1 versus S-1 alone in patients with advanced non-small-cell lung cancer

“…S-1 is an oral 5-fluorouracil (5-FU) derivative that is widely used for the treatment of various solid tumors, including NSCLC [5]. Recently, a phase 3 study of S-1 monotherapy demonstrated non-inferiority compared with docetaxel in patients with NSCLC; thus, S-1 is considered a standard chemotherapy option in East Asia [6].…”

Efficacy of Paclitaxel plus TS1 against previously treatedEGFRmutated non-small cell lung cancer

“…TS-1 combined with cisplatin or carboplatin has been studied for NSCLC. The result showed that the regimen is similar to cisplatin plus doxetaxel or carboplatin plus paclitaxel (Takeda, 2013). However, platinum combined 3rd generation chemotherapeutic agents is the standard of care for non-small cell lung cancer, which mad platinum not available in later line chemotherapy regimen (Fossella et al, 2003; Gao et al, 2009; Genova et al, 2013).…”

Intratumoral Gene Expression of Dihydrofolate Reductase and Folylpoly-C-Glutamate Synthetase Affects the Sensitivity to 5-Fluorouracil in Non-Small Cell Lung Cancer

“…is an antimetabolite that is widely used to treat various solid cancers including nonsmall cell lung cancer (NSCLC). 1,2 In Japan, an oral 5-FU prodrug has been developed. At present, UFT® and TS-1® are indicated in Japan for NSCLC and are often used as one of the drugs in postoperative adjuvant chemotherapy or systemic chemotherapy.…”

“…In addition, 5-FU anticancer agents are less effective in patients with advanced or recurrent NSCLC. 2 However, if the therapeutic effect of 5-FU anticancer drugs in cancer patients can be predicted before administration, the disadvantages of unnecessary administration can be prevented. Thus, identi cation of factors that can predict the effect of drugs before drug administration is important.…”