Abstract
Purpose
To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy.
Methods
A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m2) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1–14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level − 1), and 800/50 (Level − 2).
Results
Thirty-one patients (17 men and 14 women; median age, 70 years) were enrolled. Level 1 was chosen as the starting dose. Three of seven patients developed dose-limiting toxicities at Level 1 and the dose was de-escalated to Level − 1. Five of 12 patients developed Grade 4 neutropenia at Level − 1 and the dose was de-escalated to Level − 2. One patient developed Grade 4 neutropenia at Level − 2. Another patient was unable to receive the day 8 dose due to Grade 3 neutropenia at Level − 2. Level − 1 was confirmed as the maximum tolerated dose and Level − 2 the RD for this regimen. The 1- and 2-year recurrence-free survival rates were 77.0 and 54.0%, respectively. The recurrence-free survival rate of patients in the GS completion group was significantly higher than that of the GS discontinuation group.
Conclusions
Level − 2 was confirmed as the RD (GEM 800 mg/m2 and S-1 50 mg/m2) for GS adjuvant chemotherapy in curatively resected BTC patients without major hepatectomy.
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Acknowledgements
Acknowledgments we thank all the people related to this study, patients, caregivers, physicians, medical workers, data manager, Ms. Masami Kashibou for data management. This work was Independent Research and Development.
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Tatsuya Ioka received research funding from Taiho Pharmaceutical Co. All remaining authors declare that they have no conflict of interest.
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All procedures performed in studies involvinghuman participants were in accordance with the ethical standards ofthe institutional research committee and with the 1964 Declaration ofHelsinki and its later amendments or comparable ethical standards.
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Yanagimoto, H., Toyokawa, H., Sakai, D. et al. A phase I study for adjuvant chemotherapy of gemcitabine plus S-1 in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1202). Cancer Chemother Pharmacol 81, 461–468 (2018). https://doi.org/10.1007/s00280-017-3513-4
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DOI: https://doi.org/10.1007/s00280-017-3513-4