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01-04-2015 | Original Article

Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer

Authors: Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Makoto Yoshida, Michihiro Ono, Tsutomu Sato, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015

Abstract

Purpose

S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective phase 1 trial to determine the maximum tolerated dose (MTD) of S-1 and rates of dose-limiting toxicities (DLTs) associated with HAI of gemcitabine in patients with unresectable BTC.

Methods

BTC patients were treated with 21-day cycles of HAI of gemcitabine (1000 mg/m² on days 1 and 8) and oral S-1 (60, 70, or 80 mg/m² on days 1–14) until disease progression occurred.

Results

Fifteen patients were enrolled in the study. Grade 3 and 4 neutropenia occurred in five of 15 (33 %) patients. Among six patients who were treated with 60 mg/m² S-1, one developed grade 4 neutropenia. DLTs (grade 4 neutropenia and bladder infection) occurred in two of six patients who were treated with 70 mg/m² S-1. Two of the three patients who were treated with 80 mg/m² S-1 experienced DLTs (grade 4 leukopenia and neutropenia and grade 3 febrile neutropenia). Thus, 80 mg/m² was defined as the MTD of S-1.

Conclusion

The MTD of oral S-1 in GS therapy is 80 mg/m². Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy.

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Title: Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer
Authors: Hirotoshi Ishiwatari
Tsuyoshi Hayashi
Makoto Yoshida
Michihiro Ono
Tsutomu Sato
Koji Miyanishi
Yasushi Sato
Rishu Takimoto
Masayoshi Kobune
Junji Kato
Publication date: 01-04-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2704-0

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