title: Maintenance Therapy With Cetuximab Every Second Week in the First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-7.5 Study by the Nordic Colorectal Cancer Biomodulation Group.
abstract: BACKGROUND
  In the NORDIC-7.5 trial, how cetuximab might safely and conveniently be added to an intermittent treatment strategy in patients with prospectively selected Kirsten rat sarcoma viral oncogene homolog wild type (KRASwt) metastatic colorectal cancer (mCRC) was investigated. Patients were treated in a multicenter phase II trial with cetuximab in combination with the Nordic bolus FLOX (oxaliplatin, 5-fluorouracil, and folinic acid) for 4 months followed by maintenance cetuximab.
  
  
  METHODS
  Patients had KRASwt, nonresectable mCRC, no previous chemotherapy, and Eastern Cooperative Group performance status of 0 to 2. Patients received 8 courses of Nordic FLOX (oxaliplatin 85 mg/m(2) over 1 hour on day 1, and 5-fluorouracil 500 mg/m(2) as a bolus injection, followed 30 minutes later with bolus folinic acid 60 mg/m(2) on days 1 and 2). Cetuximab was administered every 2 weeks at a dose of 500 mg/m(2) for 16 weeks followed by cetuximab as maintenance therapy until disease progression.
  
  
  RESULTS
  Between July 2008 and September 2010, 152 KRASwt patients were included. The response rate was 62% (95% confidence interval [CI], 54%-69%), median progression-free survival was 8.0 months (95% CI, 7.5-8.9) and median overall survival was 23.2 (95% CI, 18.1-27.4) months. Twenty-one patients (14%) had later R0-resection of metastasis. FLOX with cetuximab was reintroduced in 47 of 85 patients (55%). The most common Grade 3/4 nonhematologic adverse events were diarrhea in 14 patients (9%), skin rash in 13 patients (9%), infection without neutropenia in 11 patients (7%), and fatigue in 11 patients (7%).
  
  
  CONCLUSIONS
  In a prospectively selected KRASwt population, biweekly cetuximab was safely integrated in an intermittent chemotherapy strategy and might have added to a longer chemotherapy-free interval. However, the combination of biweekly cetuximab with chemotherapy needs to be validated in trials using FOLFOX (oxaliplatin, fluorouracil, and leucovorin) or FOLFIRI (irinotecan, fluorouracil, and leucovorin).
authors.affiliation: Odense University Hospital, Odense, Denmark. Electronic address: per.pfeiffer@rsyd.dk.
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
authors.affiliation: Haukeland University Hospital, Bergen, Norway.
authors.forename: Hafdan
authors.initials: H
authors.lastname: Sorbye
authors.affiliation: Odense University Hospital, Odense, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Qvortrup
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Karlberg
authors.affiliation: Sørlandet Hospital, Kristiansand, Norway.
authors.forename: Christian
authors.initials: C
authors.lastname: Kersten
authors.affiliation: Herlev Hospital, Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Vistisen
authors.affiliation: Umeå University, Umeå, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lindh
authors.affiliation: Odense University Hospital, Odense, Denmark.
authors.forename: Jon Kroll
authors.initials: JK
authors.lastname: Bjerregaard
authors.affiliation: Uppsala University, Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil
keywords: Chemotherapy; KRAS wild type; Nordic FLOX