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World J Gastroenterol. Nov 7, 2014; 20(41): 15110-15118
Published online Nov 7, 2014. doi: 10.3748/wjg.v20.i41.15110
S-1 in the treatment of pancreatic cancer
Kentaro Sudo, Kazuyoshi Nakamura, Taketo Yamaguchi
Kentaro Sudo, Kazuyoshi Nakamura, Taketo Yamaguchi, Department of Gastroenterology, Chiba Cancer Center, Chiba 260-8717, Japan
Author contributions: Sudo K performed the literature search, performed data analysis, and wrote the manuscript; Nakamura K and Yamaguchi T performed data analysis and edited the manuscript.
Correspondence to: Kentaro Sudo, MD, PhD, Department of Gastroenterology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717, Japan. kentarosudo9@yahoo.co.jp
Telephone: +81-43-2645431 Fax: +81-43-2628680
Received: October 28, 2013
Revised: April 7, 2014
Accepted: April 30, 2014
Published online: November 7, 2014
Abstract

S-1 is an oral 5-fluorouracil (5-FU) prodrug, which is designed to improve the antitumor activity of 5-FU by inhibiting dihydropyrimidine dehydrogenase, the key enzyme of 5-FU catabolism. Recently, two important studies on the clinical use of S-1 for pancreatic cancer have been reported from Japan. In the first study (GEST study), S-1 demonstrated non-inferiority to gemcitabine (GEM) in overall survival (OS) for metastatic or locally advanced pancreatic cancer, but combination chemotherapy with GEM and S-1 did not show superiority to GEM in OS. In the second study (JASPAC-01 study), S-1 showed superiority to adjuvant chemotherapy with GEM in OS in patients with resected pancreatic cancer. In addition to GEM, S-1 is now regarded as the key drug in the management of pancreatic cancer in Japan. To date, many studies have investigated the effectiveness of S-1 in various settings, such as first-line chemotherapy for metastatic or locally advanced pancreatic cancer, second-line chemotherapy after GEM failure, and chemoradiotherapy for locally advanced disease. In this review, we focus on recent clinical trials of S-1-based chemotherapy for advanced pancreatic cancer.

Keywords: Pancreatic cancer, S-1, Chemotherapy, Randomized controlled trial, Chemoradiotherapy, Adjuvant therapy

Core tip: This review article focuses on clinical trials of S-1-based chemotherapy for advanced pancreatic cancer. Recently, S-1 has been demonstrated to be non-inferior to gemcitabine in overall survival for metastatic or locally advanced pancreatic cancer in a large-scale phase III study (GEST study). Furthermore, S-1 has been shown to be superior to adjuvant chemotherapy with gemcitabine in overall survival in patients with resected pancreatic cancer in another phase III study (JASPAC-01 study). In addition to gemcitabine, S-1 is now considered one of the key drugs in Japan.