Adenocarcinoma of the biliary system or peri-pot belly is a relatively low incidence malignancy, but its prognosis is poor with a median survival time of only 6 months if it is not surgically resectable at the time of diagnosis. Although systemic chemotherapy is recommended for patients with advanced cases that cannot be surgically resected, there is no standard chemotherapy regimen to date and the prognosis of patients does not significantly improve after chemotherapy. To date, there is a lack of randomized phase III studies with large sample sizes for the treatment of biliary system or periampullary cancers. 5-FU alone or in combination with aldehyde folate (LV) has been shown to be more than 30% effective in treating biliary system or periampullary cancers (results of small non-randomized studies), but survival has not exceeded 7 months. Because of the poor efficacy of single-agent chemotherapy, multiple combination chemotherapy regimens have been attempted for treatment. Combination chemotherapy regimens based on 5-FU or certain new drugs including epi-amycin, oxaliplatin, paclitaxel, and capecitabine have been reported to be up to 40% effective, but survival time was mostly 9 to 10 months. A retrospective analysis of 162 adenocarcinomas of the biliary system (57 intrahepatic cholangiocarcinoma, 50 gallbladder, 41 extrahepatic cholangiocarcinoma, and 14 jugular carcinoma) treated with chemotherapy with Estwan (S-1) as a single agent showed an efficiency of 13.3% and a median survival time of 6.9 months. Another multicenter phase II clinical study using S-1 monotherapy in 40 patients achieved an efficiency rate of 35.0% and a median survival time of 9.4 months. Several small sample size uncontrolled studies used oxaliplatin in combination with 5-FU/LV for adenocarcinoma of the biliary system or periampullary carcinoma with an efficiency of 18% to 20% and a median survival time of 7.0 to 9.5 months. A phase II clinical study using oxaliplatin in combination with capecitabine regimen treated 30 patients with adenocarcinoma of the small intestine or jugular abdomen with an efficacy rate of 50.0% and an overall survival time of 20.4 months. Major grade 3/4 adverse effects included malaise, peripheral neuropathy, granulocytopenia, nausea/vomiting and diarrhea. We are currently conducting a chemotherapy study for inoperable surgically resectable metastatic or locally advanced biliary system or periampullary carcinoma treated with Estwan in combination with oxaliplatin regimen (6 cycles of Estwan are provided free of charge) and initial efficacy has been observed.