title: The COMET Open-label Phase II Study of Neoadjuvant FOLFOX or XELOX Treatment Combined with Molecular Targeting Monoclonal Antibodies in Patients with Resectable Liver Metastasis of Colorectal Cancer.
abstract: Advantages of neoadjuvant chemotherapy combined with monoclonal antibodies for treating patients with resectable colorectal cancer liver metastasis (CLM) have not been established. The purpose of this study was to evaluate the efficacy and safety of oxaliplatin-based regimen (FOLFOX or XELOX) plus monoclonal antibodies (cetuximab or bevacizumab) treatment in patients with resectable CLM.
  
  
  
  A single-arm, open-label, multicenter, phase II trial was conducted for patients aged ≥ 20 years with resectable and untreated CLM. Patients received preoperative FOLFOX (6 cycles) or XELOX (4 cycles). Cetuximab or bevacizumab was administered to patients with wild-type or mutated KRAS codons 12 and 13, respectively. The primary endpoint was progression-free survival (PFS).
  
  
  
  Between January 2010 and June 2012, 47 patients were enrolled from 12 institutions. Wild-type or mutant KRAS sequences were examined in 32 and 15 patients, respectively. Twenty-one (45 %) patients experienced Grades 3/4 adverse events, and 55 % of all patients responded to therapy. The sizes of tumors of patients in the wild-type KRAS group were significantly reduced compared with those of the mutant KRAS group. The overall rates of liver resection and postoperative morbidity were 83 and 14 %, respectively, and the median PFS was 15.6 months. The median PFS times of the KRAS wild-type and mutant groups were 22.5 months and 10.5 months, respectively.
  
  
  
  Neoadjuvant therapy using FOLFOX/XELOX combined with monoclonal antibodies did not improve PFS, although it was administered safely and had less adverse effects after liver resection.
authors.affiliation: Department of Surgery, Nagoya National Hospital, Nagoya, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kataoka
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan. m-kanda@med.nagoya-u.ac.jp.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.affiliation: Department of Surgery, Konan Kosei Hospital, Konan, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ishigure
authors.affiliation: Department of Surgery, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Department of Surgery, Tosei Hospital, Seto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Surgery, Gifu Prefectural General Medical Center, Gifu, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Deguchi
authors.affiliation: Department of Surgery, Toyohashi Municipal Hospital, Toyohashi, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Mikinori
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Surgery, Yokoyama Hospital for Gastroenterological Diseases, Nagoya, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Inagaki
authors.affiliation: Department of Gastroenterological Surgery, Aichi Cancer Center Aichi Hospital, Okazaki, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Surgery, Saiseikai Matsusaka General Hospital, Matsusaka, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Takano
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Tokai Central Hospital, Gifu, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Department of Biostatistics, School of Public Health, Tokyo University Graduate School of Medicine, Tokyo, Japan.|Interfaculty Initiative in Information Studies, Tokyo University, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Department of Surgery, Nagoya National Hospital, Nagoya, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kondo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D000069287:Capecitabine / Q000008:administration & dosage; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine; D000068818:Cetuximab; D002955:Leucovorin