Kazuaki Seita1, Tomoki Ebata2, Takashi Mizuno1, Atsuyuki Maeda3, Ryuzo Yamaguchi4, Yasuhiro Kurumiya5, Eiji Sakamoto6, Kazuhiro Hiramatsu7, Masahiko Ando8, Masato Nagino1. 1. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. 2. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. tomoki@med.nagoya-u.ac.jp. 3. Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan. 4. Department of Surgery, Kasugai Municipal Hospital, Kasugai, Japan. 5. Department of Surgery, Toyota Kosei Hospital, Toyota, Japan. 6. Department of Surgery, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan. 7. Department of Surgery, Toyohashi Municipal Hospital, Toyohashi, Japan. 8. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
Abstract
BACKGROUND: Nodal metastasis is a leading attributable factor of poor survival in biliary tract cancer (BTC), and adjuvant chemotherapy targeting this high-risk feature has not been attempted to date. This study aimed to test the efficacy of adjuvant S - 1 for patients with node-positive BTC. METHODS: This single-arm multicenter phase 2 trial enrolled patients who underwent resection for histologically proven node-positive BTC. In this trial, S - 1 was administered at a dose of 80-120 mg/day on 14 days of a tri-weekly cycle for 6 months. The primary end point of the trial was 3-year overall survival (OS), in which the result would be promising if the 90% confidence interval (CI) surpassed a threshold of 30% (alpha error, 0.1; beta error, 0.2). The secondary end points were relapse-free survival (RFS), feasibility, and toxicity. RESULTS: The trial included 50 patients with perihilar (n = 23) or distal (n = 20) cholangiocarcinoma, or gallbladder cancer (n = 7). The median numbers of positive lymph nodes and examined lymph nodes were respectively 2 and 15. The 3-year OS and RFS were respectively 50% (90% CI, 40.9-59.1%) and 32.0% (95% CI, 19.1-44.9%), with median survival times of 34.6 months (95% CI, 19.3-49.8 months) and 18.4 months (95% CI, 11.9-24.9 months). Although hematologic toxicity often occurred, grades 3 and 4 toxicity were rare. The completion rate of the test therapy was 64%, and the median relative dose intensity was 87.5% (interquartile range, 50-100%). CONCLUSION: Adjuvant chemotherapy with S - 1 may be promising for patients with node-positive BTC.
BACKGROUND: Nodal metastasis is a leading attributable factor of poor survival in biliary tract cancer (BTC), and adjuvant chemotherapy targeting this high-risk feature has not been attempted to date. This study aimed to test the efficacy of adjuvant S - 1 for patients with node-positive BTC. METHODS: This single-arm multicenter phase 2 trial enrolled patients who underwent resection for histologically proven node-positive BTC. In this trial, S - 1 was administered at a dose of 80-120 mg/day on 14 days of a tri-weekly cycle for 6 months. The primary end point of the trial was 3-year overall survival (OS), in which the result would be promising if the 90% confidence interval (CI) surpassed a threshold of 30% (alpha error, 0.1; beta error, 0.2). The secondary end points were relapse-free survival (RFS), feasibility, and toxicity. RESULTS: The trial included 50 patients with perihilar (n = 23) or distal (n = 20) cholangiocarcinoma, or gallbladder cancer (n = 7). The median numbers of positive lymph nodes and examined lymph nodes were respectively 2 and 15. The 3-year OS and RFS were respectively 50% (90% CI, 40.9-59.1%) and 32.0% (95% CI, 19.1-44.9%), with median survival times of 34.6 months (95% CI, 19.3-49.8 months) and 18.4 months (95% CI, 11.9-24.9 months). Although hematologic toxicity often occurred, grades 3 and 4 toxicity were rare. The completion rate of the test therapy was 64%, and the median relative dose intensity was 87.5% (interquartile range, 50-100%). CONCLUSION: Adjuvant chemotherapy with S - 1 may be promising for patients with node-positive BTC.
Authors: Ali Belkouz; Stijn Van Roessel; Marin Strijker; Jacob L van Dam; Lois Daamen; Lydia G van der Geest; Alberto Balduzzi; Andrea Benedetti Cacciaguerra; Susan van Dieren; Quintus Molenaar; Bas Groot Koerkamp; Joanne Verheij; Elizabeth Van Eycken; Giuseppe Malleo; Mohammed Abu Hilal; Martijn G H van Oijen; Ivan Borbath; Chris Verslype; Cornelis J A Punt; Marc G Besselink; Heinz-Josef Klümpen Journal: Br J Cancer Date: 2022-01-17 Impact factor: 9.075