Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2015; 21(19): 5979-5984
Published online May 21, 2015. doi: 10.3748/wjg.v21.i19.5979
Phase I trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer
Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi
Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan
Author contributions: All the authors contributed to this work.
Ethics approval: The study was reviewed and approved by the Kitasato university hospital Institutional Review Board.
Clinical trial registration: This study is registered at Clinical research center of Kitasato university school of medicine. The registration identification number is C10-659.
Informed consent: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest: No potential conflicts of interest relevant to this article were reported.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mitsuhiro Kida MD, PhD, Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara City, Kanagawa 252-0374, Japan. m-kida@kitasato-u.ac.jp
Telephone: +81-42-778-8111 Fax: +81-42-778-9371
Received: December 18, 2014
Peer-review started: December 18, 2014
First decision: January 22, 2015
Revised: February 23, 2015
Accepted: March 31, 2015
Article in press: March 31, 2015
Published online: May 21, 2015
Processing time: 153 Days and 10.3 Hours
Abstract

AIM: To evaluate the dose-limiting toxicities (DLTs) and determine the maximum-tolerated dose (MTD) and recommended dose (RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.

METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine (mg/m2), cisplatin (mg/m2), and S-1 (mg/m2 per day) were as follows: level -1, 800/20/60; level 0, 800/25/60; level 1, 1000/25/60; and level 2, 1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15, and S-1 was administered orally twice daily on days 1 to 7 and days 15 to 21, every 4 wk.

RESULTS: Twelve patients were enrolled, and level 0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs (grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1. We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase II study.

CONCLUSION: The RD was defined as gemcitabine 1000 mg/m2 (days 1, 15), cisplatin 25 mg/m2 (days 1, 15), and S-1 80 mg/m2 per day (days 1-7, 15-21), every 4 weeks. A phase II study is planned to evaluate the effectiveness of combination chemotherapy with gemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.

Keywords: Gemcitabine; Cisplatin, S-1; Advanced biliary tract cancer

Core tip: This Phase I trial revealed that combination therapy with gemcitabine, cisplatin, and S-1 was well tolerated and feasible in patients with advanced biliary tract cancer. We are now proceeding to a phase II study to investigate the efficacy of this combination regimen in advanced biliary tract cancer.