title: EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  To determine whether adding cetuximab to irinotecan prolongs survival in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine and oxaliplatin.
  
  
  METHODS
  This multicenter, open-label, phase III study randomly assigned 1,298 patients with epidermal growth factor receptor-expressing mCRC who had experienced first-line fluoropyrimidine and oxaliplatin treatment failure to cetuximab (400 mg/m(2) day 1 followed by 250 mg/m(2) weekly) plus irinotecan (350 mg/m(2) every 3 weeks) or irinotecan alone. Primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), response rate (RR), and quality of life (QOL).
  
  
  RESULTS
  Median OS was comparable between treatments: 10.7 months (95% CI, 9.6 to 11.3) with cetuximab/irinotecan and 10.0 months (95% CI, 9.1 to 11.3) with irinotecan alone (hazard ratio [HR], 0.975; 95% CI, 0.854 to 1.114; P = .71). This lack of difference may have been due to post-trial therapy: 46.9% of patients assigned to irinotecan eventually received cetuximab (87.2% of those who did, received it with irinotecan). Cetuximab added to irinotecan significantly improved PFS (median, 4.0 v 2.6 months; HR, 0.692; 95% CI, 0.617 to 0.776; P <or= .0001) and RR (16.4% v 4.2%; P < .0001), and resulted in significantly better scores in the QOL analysis of global health status (P = .047). Cetuximab did not exacerbate toxicity, except for acneform rash, diarrhea, hypomagnesemia, and associated electrolyte imbalances. Neutropenia was the most common severe toxicity across treatment arms.
  
  
  CONCLUSIONS
  Cetuximab and irinotecan improved PFS and RR, and resulted in better QOL versus irinotecan alone. OS was similar between study groups, possibly influenced by the large number of patients in the irinotecan arm who received cetuximab and irinotecan poststudy.
authors.affiliation: Department of Medical Oncology, Ospedale San Martino, Genoa, 16132, Italy. alberto.sobrero@hsanmartino.liguria.it
authors.forename: Alberto F
authors.initials: AF
authors.lastname: Sobrero
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Werner
authors.initials: W
authors.lastname: Scheithauer
authors.forename: Yousif A
authors.initials: YA
authors.lastname: Abubakr
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Lutz
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Vega-Villegas
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
authors.forename: Ernst U
authors.initials: EU
authors.lastname: Steinhauer
authors.forename: Jana
authors.initials: J
authors.lastname: Prausova
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.forename: Gary
authors.initials: G
authors.lastname: Middleton
authors.forename: Hendrik
authors.initials: H
authors.lastname: Kröning
authors.forename: Gabriele
authors.initials: G
authors.lastname: Luppi
authors.forename: Oliver
authors.initials: O
authors.lastname: Kisker
authors.forename: Angela
authors.initials: A
authors.lastname: Zubel
authors.forename: Christiane
authors.initials: C
authors.lastname: Langer
authors.forename: Justin
authors.initials: J
authors.lastname: Kopit
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D011743:Pyrimidines; D000077150:Oxaliplatin; D000077146:Irinotecan; D066246:ErbB Receptors; D000068818:Cetuximab; D002166:Camptothecin