title: FOLFOX4 plus cetuximab administered weekly or every second week in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer: a randomized phase II CECOG study.
abstract: BACKGROUND
  This randomized phase II study investigated first-line chemotherapy plus cetuximab administered every second week in KRAS wild-type metastatic colorectal cancer.
  
  
  METHODS
  Patients received FOLFOX4 plus either standard weekly cetuximab (arm 1) or cetuximab (500 mg/m(2)) every second week (arm 2), until disease progression or unacceptable toxicity. Primary end point was the objective response rate (ORR). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were also investigated. The study was not powered to establish non-inferiority, but aimed at the estimation of treatment differences.
  
  
  RESULTS
  Of 152 randomized eligible patients, 75 were treated in arm 1 and 77 in arm 2; ORRs [53% versus 62%, odds ratio 1.40, 95% confidence interval (CI) 0.74-2.66], PFS [median 9.5 versus 9.2 months, hazard ratio (HR) 0.92, 95% CI 0.63-1.34], OS (median 25.8 versus 23.0 months, HR 0.86, 95% CI 0.56-1.30) and DCR (87%) were comparable. HRs adjusted for baseline factors were 1.01 and 0.99 for PFS and OS, respectively. Frequencies of grade 3/4 adverse events in arms 1 versus 2 were similar: most common were neutropenia (28% versus 34%) and rash (15% versus 17%).
  
  
  CONCLUSIONS
  Activity and safety of FOLFOX4 plus either cetuximab administered weekly or every second week were similar.
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna; Comprehensive Cancer Centre, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Brodowicz
authors.affiliation: Institutul Oncologic, Cluj Napoca, Romania.
authors.forename: T E
authors.initials: TE
authors.lastname: Ciuleanu
authors.affiliation: Institute for Oncology and Radiology, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Radosavljevic
authors.affiliation: Division of Oncology, Tel Aviv Souraski Medical Center, Tel Aviv, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Shacham-Shmueli
authors.affiliation: Department of Oncology, University Hospital Zagreb/Rebro, Zagreb, Croatia.
authors.forename: D
authors.initials: D
authors.lastname: Vrbanec
authors.affiliation: The Latvian Center of Oncology, Riga, Latvia.
authors.forename: S
authors.initials: S
authors.lastname: Plate
authors.affiliation: Department of Medical Oncology, University Hospital for Tumors, Zagreb, Croatia.
authors.forename: Z
authors.initials: Z
authors.lastname: Mrsic-Krmpotic
authors.affiliation: Radiology Clinic, Semmelweis University, Budapest, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Dank
authors.affiliation: P Stradins University Hospital, Riga, Latvia.
authors.forename: G
authors.initials: G
authors.lastname: Purkalne
authors.affiliation: Biometrics, IST GmbH, Mannheim, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Messinger
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna; Comprehensive Cancer Centre, Vienna, Austria. Electronic address: christoph.zielinski@meduniwien.ac.at.
authors.forename: C C
authors.initials: CC
authors.lastname: Zielinski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil
keywords: FOLFOX4; KRAS wild-type; cetuximab every second week; metastatic colorectal cancer