A prospective feasibility study of one-year administration of adjuvant S-1 therapy for resected biliary tract cancer in a multi-institutional trial (Tokyo Study Group for Biliary Cancer: TOSBIC01)

Osamu Itano,Norihiro Kishida,Junichi Matsui,Yuta Abe,Go Oshima,Shigeo Hayatsu,Tadayuki Sakuragawa,Ken Ikeda,Masaya Shito,Shutaro Hori,Hiroharu Shinozaki,Shigenori Ei,Masatsugu Ishii,Masahiro Shinoda,Yusuke Takemura,Minoru Kitago,Koichi Aiura,Eiji Tamagawa,Keiichi Suzuki,Takuya Minagawa,Hidejiro Urakami,Kiminori Takano,Hiroshi Yagi,Hiroto Fujisaki,Yuko Kitagawa

doi:10.1186/s12885-020-07185-6

Abstract

BackgroundAlthough surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial.MethodsThe inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m2/day orally twice daily on days 1–28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS).ResultsForty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events.ConclusionsOne-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing.Trial registrationUMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347

Highlights

Surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory
A meta-analysis series has shown the potential benefit of adjuvant chemotherapy, especially for patients with node-positive resected biliary tract cancer [6]
In this study, we evaluated the feasibility of adjuvant chemotherapy by assessing the outcomes of 1-year administration of S-1 for resected BTC

Summary

Introduction

Surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. Biliary tract cancer (BTC) includes intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and ampulla of Vater carcinoma. A meta-analysis series has shown the potential benefit of adjuvant chemotherapy, especially for patients with node-positive resected biliary tract cancer [6]. No prior randomized control trial (RCT) proved the positive effect of postoperative adjuvant chemotherapy in patients with BTC [7, 8]. A RCT assessing a 6-month administration of capecitabine for adjuvant therapy for BTC demonstrated improvements in survival [9]; the optimal adjuvant chemotherapy regimen for resected BTC has not yet been standardized

Methods

Results

Conclusion