Original Article

Cancer Chemotherapy and Pharmacology

, Volume 69, Issue 5, pp 1181-1188

First online:

Phase I trial of oral S-1 combined with gemcitabine and cisplatin for advanced biliary tract cancer (KHBO1002)

  • Masashi KanaiAffiliated withOutpatient Oncology Unit, Kyoto University Hospital Email author 
  • , Etsuro HatanoAffiliated withDepartment of Surgery, Graduate School of Medicine, Kyoto University Hospital
  • , Syogo KobayashiAffiliated withDepartment of Surgery, Graduate School of Medicine, Osaka University
  • , Yutaka FujiwaraAffiliated withDepartment of Medical Oncology and Hematology, Kobe University Graduate School of Medicine
  • , Daisuke SakaiAffiliated withDepartment of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University
  • , Yuzo KodamaAffiliated withDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University Hospital
  • , Tetsuo AjikiAffiliated withDepartment of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine
  • , Hiroaki NaganoAffiliated withDepartment of Surgery, Graduate School of Medicine, Osaka University
  • , Tatsuya IokaAffiliated withOsaka Medical Center for Cancer and Cardiovascular Diseases

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Purpose

We aimed to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the addition of S-1, an oral fluorouracil derivative, to gemcitabine and cisplatin combination therapy, which is the current standard treatment for advanced biliary tract cancer.

Methods

Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were eligible for inclusion. The planned dosages of gemcitabine (mg/m2)/cisplatin (mg/m2)/S-1 (mg/m2/day) were as follows: level 0, 800/25/60; level 1, 1,000/25/60; and levels 2 and 3, 1,000/25/80. In each cycle, gemcitabine and cisplatin were intravenously administered on day 1 (or days 1 and 8 at level 3), and S-1 was orally administered twice daily on days 1–7 (or days 1–14 at level 3); this was repeated every 14 days (or 21 days at level 3).

Results

Seventeen patients were enrolled, and level 1 was chosen as the starting dose. Two of six patients developed DLTs (grade 4 neutropenia and grade 3 febrile neutropenia) at level 1, and the dose was escalated to level 2. DLTs (grade 3 rashes and grade 3 vasovagal reactions) occurred in two of six assessable patients at level 2; we then proceeded to level 3. The first three assessable patients enrolled at level 3 developed DLTs (two cases of grade 4 neutropenia, one of grade 4 leucopenia, two of grade 3 fatigue, one of grade 3 anorexia, and one of grade 3 febrile neutropenia) during their first cycle, and this dose was determined to be the MTD. Therefore, we selected level 2 as the recommended dose (RD) for a subsequent phase II study.

Conclusions

We determined the RD of gemcitabine/cisplatin/S-1 combination therapy for advanced biliary tract cancer; we are proceeding to a phase II study to investigate the efficacy of this combination therapy for advanced biliary tract cancer.

Keywords

S-1 Gemcitabine Cisplatin Biliary tract cancer