title: Multicenter randomized phase II clinical trial of oxaliplatin reintroduction as a third- or later-line therapy for metastatic colorectal cancer-biweekly versus standard triweekly XELOX (The ORION Study).
abstract: BACKGROUND
  The aim of this multicenter, open-label, randomized phase II trial was to evaluate the efficacy of a dose-dense capecitabine and oxaliplatin (XELOX) regimen in patients with metastatic colorectal cancer (mCRC) for whom reintroduction of oxaliplatin had been planned as a third- or later-line regimen.
  
  
  METHODS
  The patients with mCRC who had received prior chemotherapy including oxaliplatin and were scheduled for reintroduction of oxaliplatin were randomized to capecitabine (1,000 mg/m(2)) twice daily on days 1-14 and oxaliplatin (130 mg/m(2)) on day 1 every 21 days (Q3W group) or capecitabine (2,000 mg/m(2)) twice daily on days 1-7 and oxaliplatin (85 mg/m(2)) on day 1 every 14 days (Q2W group). The primary endpoint was the time-to-treatment failure (TTF). Other endpoints included overall survival (OS), progression-free survival (PFS) and other adverse events (AEs).
  
  
  RESULTS
  A total of 46 patients were enrolled in the trial-22 patients were randomly assigned to the Q3W group and 23 to the Q2W group. The median TTF was 3.4 months in both groups (hazard ratio [HR] 1.053; p = 0.880). The median PFS and OS were 3.3 and 9.2 months in the Q2W group and 4.3 and 12.1 months in the Q3W group, respectively (HR 1.15; p = 0.153 and 0.672; p = 0.836). The most common grade 3-4 AEs in the Q3W and Q2W groups were fatigue (27.3 vs 21.7), neuropathy (9.1 vs 0 %) and diarrhea (9.1 vs 0 %), respectively.
  
  
  CONCLUSIONS
  There was no significant inter-group difference in any of the efficacy and safety endpoints, including TTF, OS, RFS and AEs. The results of this clinical trial were convincingly negative.
authors.affiliation: Department of Surgery, Osaka General Medical Center, Osaka, Japan.
authors.forename: Chu
authors.initials: C
authors.lastname: Matsuda
authors.affiliation: Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan. michitaka.honda@jfcr.or.jp.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Honda
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, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Fukunaga
authors.affiliation: Department of Surgery, Saitama Medical University, Saitama, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Surgery, Fukui Saiseikai Hospital, Fukui, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Munemoto
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Osaka, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Surgery, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Bando
authors.affiliation: Department of Surgery, Toho University, Sakura Hospital, Sakura, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Oshiro
authors.affiliation: Department of Surgery, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Surgery, Japan Post Kyoto Teishin Hospital, Kyoto, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Tokunaga
authors.affiliation: Department of Surgery, Rinku General Medical Center, Osaka, Japan.
authors.forename: Akitomo
authors.initials: A
authors.lastname: Fujii
authors.affiliation: Kitakyushu General Hospital, Kitakyushu, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Department of Epidemiology & Biostatistics, University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Clinical Cancer Center, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009422:Nervous System Diseases / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D010071:Oxaloacetates; D019233:Retreatment; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil
keywords: Metastatic colorectal cancer; Oxaliplatine; Reintroduction