Summary
Purpose A 3 week treatment schedule consisting of 2 weeks of S-1 therapy and 1 week of no therapy was introduced to reduce the toxicity and increase the convenience of combination chemotherapy. Hepatic dysfunction (HD) is common in patients with biliary tract cancer. A phase I study was conducted to assess the effects of a 3 week treatment schedule in Asian patients with or without HD. Methods Forty-six patients were stratified into four groups, according to the HD criteria of the National Cancer Institute Organ Dysfunction Working Group. A three dose escalation schema was used. Results In the normal hepatic function group, two dose-limiting toxicity (DLT) events occurred among 12 patients at the prespecified maximal dose of 100 mg/m2/day. This dose was thereby established as the maximal tolerable dose (MTD). No DLT events were observed at the predefined maximal dose of 80 mg/m2/day in the mild HD group. In the moderate HD group, two DLT events occurred among five patients treated with 80 mg/m2/day, and the MTD was defined as 70 mg/m2/day. Two of six subjects in the severe HD group experienced DLT events at doses of 60 mg/m2/day and none developed DLT events at 50 mg/m2/day. Conclusions The MTDs for a 3 week schedule of S-1 treatment were defined in patients with or without hepatic dysfunction. A 3 week treatment regimen of S-1 might be a platform for combination with newer cytotoxic agents or biologics.
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Acknowledgements
This manuscript was presented in part at the 15th Congress of the European Cancer Organisation (ECCO) and the 34th Multidisciplinary Congress of the European Society for Medical Oncology (ESMO) in Berlin, Germany, from September 20 to 24, 2009. This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare and Family Affairs, R.O.K. (A030001, A062254) and the Asan Institute for Life Sciences (Seoul, Republic of Korea, 2006–231).
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Dok Hyun Yoon and Hyo Jung Lee contributed equally to the work as the first authors.
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Yoon, D.H., Lee, H.J., Hong, Y.S. et al. A phase I study of S-1 treatment with a 3 week schedule in advanced biliary cancer patients with or without hepatic dysfunction. Invest New Drugs 29, 332–339 (2011). https://doi.org/10.1007/s10637-009-9378-6
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DOI: https://doi.org/10.1007/s10637-009-9378-6