Erschienen in:
01.04.2015 | Original Article
Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer
verfasst von:
Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Makoto Yoshida, Michihiro Ono, Tsutomu Sato, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato
Erschienen in:
Cancer Chemotherapy and Pharmacology
|
Ausgabe 4/2015
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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.