Nakata et al. Journal of Experimental & Clinical Cancer Research 2010, 29:15 http://www.jeccr.com/content/29/1/15 R E S E A R C H Open Access Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer Bunzo Nakata*, Ryosuke Amano, Shigetomi Nakao, Tatsuro Tamura, Osamu Shinto, Toshiki Hirakawa, Yoshihiro Okita, Nobuya Yamada, Kosei Hirakawa Abstract Background: The combination of gemcitabine (GEM) and S-1, an oral 5-fluorouracil (5-FU) derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. Methods: Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK) study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed. Results: The maximum concentration (Cmax), the area under the curve from the drug administration to the infinite time (AUCinf), and the elimination half-life (T1/2) of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax) were not significantly different between S-1 administration with and without GEM. Conclusion: There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU. Background Unresectable pancreatic cancer is known to have a poor prognosis, with most patients dying within several months of diagnosis. However, recent progress in che- motherapy using gemcitabine (GEM) for this disease has improved patient survival. A number of phase III clinical trials have been performed to determine the GEM regi- mens that lead to the greatest increases in survival com- pared with GEM monotherapy. To date, only one regimen has been shown to yield significantly longer survival periods than GEM alone in phase III studies: GEM with erlotinib, an epidermal growth factor recep- tor (EGFR)-targeting agent [1]. S-1 is an oral fluoropyrimidine derivative that contains tegafur (a 5-FU prodrug) and a reversible competitive dihydropyrimidine dehydrogenase (DPD) inhibitor, 5- chloro-2,4-dihydrogenase (CDHP). As DPD is a rate- * Correspondence: bunzo@med.osaka-cu.ac.jp Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan limiting enzyme that degrades 5-FU, CDHP is expected to enhance the cytotoxicity of 5-FU by prolonging high 5-FU concentrations in blood and tumor tissues [2]. In Japan, S-1 has been clinically used as a first-line che- motherapeutic agent for pancreatic cancer since being approved for national health insurance coverage in 2006. A phase II study of S-1 for 40 patients with meta- static pancreatic cancers resulted in the response rate of 37.5% and the overall survival time of 9.2 months [3]. As the efficacy of S-1 monotherapy against pancreatic cancer is not satisfactory, numerous studies using S-1 combined with GEM have been conducted. Two phase I studies and two phase II studies of the combination therapy showed promising efficacy and acceptable adverse events [4-7]. A phase III study comparing GEM +S-1 vs. S-1 monotherapy vs. GEM monotherapy for metastatic pancreatic cancer (GEST study) has been underway in Japan and Taiwan since 2007. In contrast to the large number of clinical trials regarding GEM+S- 1, pharmacokinetic studies to investigate the interaction © 2010 Nakata et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.