Masaru Matsumura1, Kiyoshi Hasegawa2, Masaru Oba1, Kensei Yamaguchi3, Hiroyuki Uetake4, Takayuki Yoshino5, Satoshi Morita6, Keiichi Takahashi7, Michiaki Unno8, Yasuhiro Shimada9, Kei Muro10, Nobuhisa Matsuhashi11, Masaki Mori12, Hideo Baba13, Mitsuo Shimada14, Yoshihiro Mise15, Yoshikuni Kawaguchi1, Tatsuo Kagimura16, Kiyoshi Ishigure17, Akio Saiura15, Kenichi Sugihara18, Norihiro Kokudo19. 1. Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. 2. Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. kihase-tky@umin.ac.jp. 3. Department of Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake Hospital, Tokyo, Japan. 4. Department of Clinical Research, National Disaster Medical Center, Tokyo, Japan. 5. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 6. Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 7. Department of Surgery, Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, Tokyo, Japan. 8. Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan. 9. Department of Clinical Oncology, Kochi Health Sciences Center, Kochi, Japan. 10. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 11. Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan. 12. Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, and School of Medicine, Tokai University, Isehara, Japan. 13. Department of Gastroenterological Surgery, Graduate School of Medicine, Kumamoto University, Kumamoto, Japan. 14. Department of Digestive and Pediatric Surgery, Graduate School of Medicine, Tokushima University, Tokushima, Japan. 15. Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan. 16. Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan. 17. Department of Surgery, Konan Kosei Hospital, Nagoya, Japan. 18. Tokyo Medical and Dental University, Tokyo, Japan. 19. Department of Surgery, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
Abstract
PURPOSE: To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM. METHODS: Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS). RESULTS: There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69-2.01], P = 0.539: OS, 1.03 [0.46-2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS. CONCLUSION: There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).
PURPOSE: To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM. METHODS: Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS). RESULTS: There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69-2.01], P = 0.539: OS, 1.03 [0.46-2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS. CONCLUSION: There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).
Authors: Bernard Nordlinger; Halfdan Sorbye; Bengt Glimelius; Graeme J Poston; Peter M Schlag; Philippe Rougier; Wolf O Bechstein; John N Primrose; Euan T Walpole; Meg Finch-Jones; Daniel Jaeck; Darius Mirza; Rowan W Parks; Murielle Mauer; Erik Tanis; Eric Van Cutsem; Werner Scheithauer; Thomas Gruenberger Journal: Lancet Oncol Date: 2013-10-11 Impact factor: 41.316
Authors: N Ayez; E P van der Stok; D J Grünhagen; J Rothbarth; E van Meerten; A M Eggermont; C Verhoef Journal: Eur J Surg Oncol Date: 2015-05-02 Impact factor: 4.424
Authors: Jean-Nicolas Vauthey; Timothy M Pawlik; Dario Ribero; Tsung-Teh Wu; Daria Zorzi; Paulo M Hoff; Henry Q Xiong; Cathy Eng; Gregory Y Lauwers; Mari Mino-Kenudson; Mauro Risio; Andrea Muratore; Lorenzo Capussotti; Steven A Curley; Eddie K Abdalla Journal: J Clin Oncol Date: 2006-05-01 Impact factor: 44.544
Authors: Yoshikuni Kawaguchi; Heather A Lillemoe; Elena Panettieri; Yun Shin Chun; Ching-Wei D Tzeng; Thomas A Aloia; Scott Kopetz; Jean-Nicolas Vauthey Journal: J Am Coll Surg Date: 2019-05-02 Impact factor: 6.113
Authors: Gunnar Folprecht; Thomas Gruenberger; Wolf O Bechstein; Hans-Rudolf Raab; Florian Lordick; Jörg T Hartmann; Hauke Lang; Andrea Frilling; Jan Stoehlmacher; Jürgen Weitz; Ralf Konopke; Christian Stroszczynski; Torsten Liersch; Detlev Ockert; Thomas Herrmann; Eray Goekkurt; Fabio Parisi; Claus-Henning Köhne Journal: Lancet Oncol Date: 2009-11-26 Impact factor: 41.316
Authors: Bernard Nordlinger; Halfdan Sorbye; Bengt Glimelius; Graeme J Poston; Peter M Schlag; Philippe Rougier; Wolf O Bechstein; John N Primrose; Euan T Walpole; Meg Finch-Jones; Daniel Jaeck; Darius Mirza; Rowan W Parks; Laurence Collette; Michel Praet; Ullrich Bethe; Eric Van Cutsem; Werner Scheithauer; Thomas Gruenberger Journal: Lancet Date: 2008-03-22 Impact factor: 79.321