A phase I study of S-1 treatment with a 3 week schedule in advanced biliary cancer patients with or without hepatic dysfunction

作者：Yoon Dok Hyun; Lee Hyo Jung; Hong Yong Sang; Kim Kyu pyo; Lee Sung Sook; Lee Jae Lyun; Chang Heung Moon; Ryu Min Hee; Kang Yoon Koo; Lee Jung Shin; Kim Tae Won^*

来源：Investigational New Drugs, 2011, 29(2): 332-339.

DOI：10.1007/s10637-009-9378-6

• S-1
• 3 week schedule
• Phase I
• Hepatic dysfunction

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 dysHD) 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/m(2)/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/m(2)/day in the mild HD group. In the moderate HD group, two DLT events occurred among five patients treated with 80 mg/m(2)/day, and the MTD was defined as 70 mg/m(2)/day. Two of six subjects in the severe HD group experienced DLT events at doses of 60 mg/m(2)/day and none developed DLT events at 50 mg/m(2)/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.

• 出版日期2011-4