title: Phase II trial of neoadjuvant chemotherapy with S-1 and oxaliplatin plus bevacizumab for colorectal liver metastasis (N-SOG 05 trial).
abstract: OBJECTIVE
  This Phase II trial evaluated the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 and oxaliplatin (SOX) plus bevacizumab (Bev) in patients with colorectal liver metastasis (CRLM).
  
  
  METHODS
  Patients with initially resectable CRLM received four cycles of SOX plus Bev as NAC. We adopted the R0 resection rate as the primary endpoint, and the threshold R0 resection rate was set at 80%.
  
  
  RESULTS
  Between December 2010 and August 2014, 61 patients were enrolled in this study and all started NAC. The completion rate of NAC was 82.0%. Three patients (4.9%) developed severe liver dysfunction caused by NAC and one patient finally decided against resection. Three patients (4.9%) were judged as having progressive disease during or after NAC and did not undergo liver resection. Among 57 patients who underwent liver resection after NAC, three patients were diagnosed with CRLM by pre-treatment imaging modalities and received NAC although a final pathological diagnosis was another malignant disease or benign condition. Finally, 47 of the 54 patients (87.0%) with resected CRLM achieved R0 resection. The pathological complete response rate of the 54 patients was 13.0%, and 31.5% were judged as pathological responders. However, the R0 resection rate of 77.0% in the entire cohort did not meet the endpoint.
  
  
  CONCLUSIONS
  NAC with SOX plus Bev has an acceptable toxicity profile and achieved a satisfactory pathological response. However, accuracy of pre-operative diagnoses and liver dysfunction caused by NAC were serious problems. Easy introduction of NAC for initially resectable CRLM should not be performed.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mukai
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Uehara
authors.affiliation: Department of Surgery, Anjo Kosei Hospital, Aichi.
authors.forename: Hidenari
authors.initials: H
authors.lastname: Goto
authors.affiliation: Department of Surgery, Toyohashi Municipal Hospital, Aichi.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hiramatsu
authors.affiliation: Department of Surgery, Toyota Kosei Hospital.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Surgery, Nagoya Daini Red Cross Hospital, Nagoya.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sakamoto
authors.affiliation: Department of Surgery, Ogaki Municipal Hospital, Gifu.
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Department of Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya.
authors.forename: Eiji
authors.initials: E
authors.lastname: Takeuchi
authors.affiliation: Department of Surgery, Handa City Hospital, Aichi, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ebata
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya.
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid
keywords: S-1; bevacizumab; colorectal cancer; liver metastasis; neoadjuvant chemotherapy; oxaliplatin