title: Multicenter Phase II study of FOLFOX or biweekly XELOX and Erbitux (cetuximab) as first-line therapy in patients with wild-type KRAS/BRAF metastatic colorectal cancer: The FLEET study.
abstract: BACKGROUND
  The clinical benefit of cetuximab combined with oxaliplatin-based chemotherapy remains under debate. The aim of the present multicenter open-label Phase II study was to explore the efficacy and safety of biweekly administration of cetuximab and mFOLFOX-6 or XELOX as first-line chemotherapy in patients with metastatic colorectal cancer.
  
  
  METHODS
  Sixty-two patients with previously untreated KRAS/BRAF wild-type metastatic colorectal cancer were recruited to the study between April 2010 and May 2011. Patients received one of two treatment regimens, either cetuximab plus mFOLFOX-6 (FOLFOX + Cmab) or cetuximab plus biweekly XELOX (XELOX + Cmab), according to their own preference. Treatment was continued until disease progression or the appearance of intolerable toxicities. The primary endpoint was response rate; secondary endpoints were progression-free survival, overall survival, disease control rate, dose intensity, conversion rate to surgical resection, and safety.
  
  
  RESULTS
  The response rates in the FOLFOX + Cmab (n = 37) and XELOX + Cmab (n = 25) groups were 64.9 % (24/37) and 72.0 % (18/25), respectively. The median PFS in the FOLFOX + Cmab and XELOX + Cmab groups was 13.1 months (95 % confidence interval [CI] 12.1-17.5) and 13.4 months (95 % CI 10.1-17.9), respectively. Neutropenia was the most frequent grade 3/4 adverse event in both groups (33.9 %), followed by anorexia, acneiform eruption, skin fissure and paronychia. A waterfall plot of tumor diameter showed prominent shrinkage of the tumors in 88.7 % of patients.
  
  
  CONCLUSIONS
  The results of the present study indicate that biweekly cetuximab plus mFOLFOX-6/XELOX is an effective and tolerable treatment regimen. Biweekly administration of cetuximab requires only one hospital visit every 2 weeks, and may become a convenient treatment option for patients with KRAS/BRAF wild-type metastatic colorectal cancer.
  
  
  BACKGROUND
  This study is registered with University Hospital Medical Information Network (UMIN 000003253 ). Registration date is 02/24/2010.
authors.affiliation: Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan. h-sodasoda@outlook.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Soda
authors.affiliation: Cancer Treatment Center, Kochi Medical School Hospital, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan. hmaeda@kochi-u.ac.jp.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Osaka Rosai Hospital, Sakai, Japan. j-hasegawa@orh.go.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: Department of Surgical Oncology, Gifu University Hospital, Gifu, Japan. takaota@gifu-u.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University, Graduate School of Medicine, Ube, Japan. hazama@yamaguchi-u.ac.jp.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.affiliation: Sakai City Hospital, Sakai, Japan. fukunaga1404@hp.pref.hyogo.jp.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Fukunaga
authors.affiliation: Japan Community Health care Organization Osaka Hospital, Osaka, Japan. konoemiko6@gmail.com.
authors.forename: Emiko
authors.initials: E
authors.lastname: Kono
authors.affiliation: Sano Hospital, Kobe, Japan. tomomakotaka6410@yahoo.co.jp65.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kotaka
authors.affiliation: Tokai Central Hospital, Kakamigahara, Japan. sakamjun@med.nagoya-u.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Kitakyushu General Hospital, Kitakyushu, Japan. n-nagata@oboe.ocn.ne.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. oba@epistat.m.u-tokyo.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Aichi Medical University, Nagakute, Japan. hmishima@aichi-med-u.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D010071:Oxaloacetates; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D003841:Deoxycytidine; D000069287:Capecitabine; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil