Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

Bunzo Nakata,Osamu Shinto,Toshiki Hirakawa,Yoshihiro Okita,Nobuya Yamada,Tatsuro Tamura,Kosei Hirakawa,Shigetomi Nakao,Ryosuke Amano

doi:10.1186/1756-9966-29-15

Abstract

BackgroundThe 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.MethodsSix 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.ResultsThe 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.ConclusionThere were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.

Highlights

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
Unresectable pancreatic cancer is known to have a poor prognosis, with most patients dying within several months of diagnosis
A number of phase III clinical trials have been performed to determine the GEM regimens that lead to the greatest increases in survival compared with GEM monotherapy

Summary

Introduction

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. Unresectable pancreatic cancer is known to have a poor prognosis, with most patients dying within several months of diagnosis. A number of phase III clinical trials have been performed to determine the GEM regimens that lead to the greatest increases in survival compared with GEM monotherapy. 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 receptor (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, 5chloro-2,4-dihydrogenase (CDHP).

Methods

Results

Conclusion