Suguru Yamada1, Tsutomu Fujii2, Tomohisa Yamamoto3, Hideki Takami1, Isaku Yoshioka2, So Yamaki3, Fuminori Sonohara1, Kazuto Shibuya2, Fuyuhiko Motoi4, Satoshi Hirano5, Yoshiak Murakami6, Hitoshi Inoue7, Masamichi Hayashi1, Daisuke Hashimoto3, Kenta Murotani8, Joji Kitayama9, Hideki Ishikawa10, Yasuhiro Kodera1, Mitsugu Sekimoto3, Sohei Satoi3. 1. Nagoya University Graduate School of Medicine, Gastroenterological Surgery, Nagoya, Japan. 2. Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan. 3. Department of Surgery, Kansai Medical University, Hirakata, Japan. 4. Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. 5. Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 6. Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan. 7. Department of HBP and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan. 8. Biostatistics Centre, Graduate School of Medicine, Kurume University, Fukuoka, Japan. 9. Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan. 10. Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies globally. We have previously explored the clinical efficacy of intraperitoneal (IP) paclitaxel therapy for patients with PDAC and peritoneal metastasis, which demonstrated favourable response and disease control rates. However, the real implications of conversion surgery after IP therapy remain unclear. METHODS: We conducted two multicenter clinical trials of IP therapy with paclitaxel in patients with PDAC and peritoneal metastasis. We focused on patients who underwent conversion surgery and investigated the long-term outcomes, particularly, initial recurrence patterns and long-term survival. RESULTS: Seventy-nine patients with PDAC and peritoneal metastasis were treated, and 33 (41.8%) patients received SP (intravenous IP paclitaxel with S-1) and 46 (58.3%) were administered GAP (intravenous gemcitabine + nab-paclitaxel combined with IP paclitaxel) combination therapy. Of the 79 patients, 16 (20.3%) underwent conversion surgery. The median time to surgery was 9.0 (range, 4.1-13.0) months after the initiation of chemotherapy. Finally, 13 (81.3%) patients underwent R0 resection. Evans grade was IIA in nine patients, IIB in four patients, III in two patients, and IV in one patient. The median overall survival time in patients who underwent conversion surgery was 32.5 (range, 13.5-66.9) months. Twelve (75.0%) patients were found to have experienced recurrence after conversion surgery. Especially, peritoneal recurrence was observed in 50% of patients as the initial recurrence pattern. The median recurrence-free survival time was 9.2 (range, 5.1-32.8) months, and three patients have survived without recurrence to date. CONCLUSIONS: Our IP therapy displays promising clinical efficacy with acceptable tolerability in patients with PDAC and peritoneal metastasis. Although we could observe some super-responders in the cohort, further improvements in IP therapy are warranted. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies globally. We have previously explored the clinical efficacy of intraperitoneal (IP) paclitaxel therapy for patients with PDAC and peritoneal metastasis, which demonstrated favourable response and disease control rates. However, the real implications of conversion surgery after IP therapy remain unclear. METHODS: We conducted two multicenter clinical trials of IP therapy with paclitaxel in patients with PDAC and peritoneal metastasis. We focused on patients who underwent conversion surgery and investigated the long-term outcomes, particularly, initial recurrence patterns and long-term survival. RESULTS: Seventy-nine patients with PDAC and peritoneal metastasis were treated, and 33 (41.8%) patients received SP (intravenous IP paclitaxel with S-1) and 46 (58.3%) were administered GAP (intravenous gemcitabine + nab-paclitaxel combined with IP paclitaxel) combination therapy. Of the 79 patients, 16 (20.3%) underwent conversion surgery. The median time to surgery was 9.0 (range, 4.1-13.0) months after the initiation of chemotherapy. Finally, 13 (81.3%) patients underwent R0 resection. Evans grade was IIA in nine patients, IIB in four patients, III in two patients, and IV in one patient. The median overall survival time in patients who underwent conversion surgery was 32.5 (range, 13.5-66.9) months. Twelve (75.0%) patients were found to have experienced recurrence after conversion surgery. Especially, peritoneal recurrence was observed in 50% of patients as the initial recurrence pattern. The median recurrence-free survival time was 9.2 (range, 5.1-32.8) months, and three patients have survived without recurrence to date. CONCLUSIONS: Our IP therapy displays promising clinical efficacy with acceptable tolerability in patients with PDAC and peritoneal metastasis. Although we could observe some super-responders in the cohort, further improvements in IP therapy are warranted. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: G Paul Wright; Katherine E Poruk; Mazen S Zenati; Jennifer Steve; Nathan Bahary; Melissa E Hogg; Amer H Zuriekat; Christopher L Wolfgang; Herbert J Zeh; Matthew J Weiss Journal: J Gastrointest Surg Date: 2016-09-07 Impact factor: 3.452
Authors: H Ishigami; J Kitayama; S Kaisaki; A Hidemura; M Kato; K Otani; T Kamei; D Soma; H Miyato; H Yamashita; H Nagawa Journal: Ann Oncol Date: 2009-07-15 Impact factor: 32.976
Authors: S Yamada; T Fujii; T Yamamoto; H Takami; I Yoshioka; S Yamaki; F Sonohara; K Shibuya; F Motoi; S Hirano; Y Murakami; H Inoue; M Hayashi; K Murotani; J Kitayama; H Ishikawa; Y Kodera; M Sekimoto; S Satoi Journal: Br J Surg Date: 2020-07-07 Impact factor: 6.939