title: A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer.
abstract: BACKGROUND
  This phase II trial evaluated the efficacy and safety of cetuximab combined with FOLFOX6 (leucovorin [LV] 5-fluorouracil [5-FU]/oxaliplatin) in the first-line treatment of patients with advanced or metastatic colorectal cancer.
  
  
  METHODS
  Patients with locally advanced or metastatic CRC who had received no previous therapy for advanced disease were treated with cetuximab at a loading dose of 400 mg/m2 followed by 250 mg/m2 weekly and a FOLFOX6 regimen every 2 weeks consisting of oxaliplatin 85 mg/m2, LV 400 mg/m2, and 5-FU bolus 400 mg/m2 followed by 5-FU continuous infusion 2400 mg/m2 over 46 hours.
  
  
  RESULTS
  A total of 82 eligible patients were enrolled; epidermal growth factor receptor expression was positive in 67 patients. The overall response rate was 44.8%. In addition, 30 patients (44.8%) in the evaluable population experienced stable disease. Median time to progression or death was 9.3 months (95% CI, 7.0-11.3 months), and median survival was 21.7 months (95% CI, 17.5-27.8 months). Patients who experienced skin toxicity had a statistically significant and longer median survival time than those patients with no skin toxicity (P = .0001). The most commonly observed toxicities were neutropenia (65%), fatigue (56.3%), diarrhea (53.8%), nausea (50%), acneiform rash (41.3%), and stomatitis (35%).
  
  
  CONCLUSIONS
  Our results demonstrate that cetuximab can be safely combined with FOLFOX6 for the first-line treatment of patients with metastatic CRC (mCRC). The efficacy parameters are similar to other first-line regimens in mCRC. Because of the emergence of KRAS as a predictive marker, this regimen has promise in KRAS wild-type mCRC.
authors.affiliation: Center for Cancer and Blood Disorders, Bethesda, MD 20817, USA. rboccia@ccbdmd.com
authors.forename: Ralph V
authors.initials: RV
authors.lastname: Boccia
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Cosgriff
authors.forename: David L
authors.initials: DL
authors.lastname: Headley
authors.forename: Suprith
authors.initials: S
authors.lastname: Badarinath
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016001:Confidence Intervals; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D014481:United States; D018631:ras Proteins
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil