title: Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first-line treatment for patients with metastatic colorectal cancer: AIO KRK-0104--a randomized trial of the German AIO CRC study group.
abstract: OBJECTIVE
  The AIO KRK-0104 randomized phase II trial investigated the efficacy and safety of cetuximab combined with capecitabine and irinotecan (CAPIRI) or capecitabine and oxaliplatin (CAPOX) in the first-line treatment of metastatic colorectal cancer (mCRC).
  
  
  METHODS
  A total of 185 patients with mCRC were randomly assigned to cetuximab (400 mg/m(2) day 1, followed by 250 mg/m(2) weekly) plus CAPIRI (irinotecan 200 mg/m(2), day 1; capecitabine 800 mg/m(2) twice daily days 1 through 14, every 3 weeks; or cetuximab plus CAPOX (oxaliplatin 130 mg/m(2) day 1; capecitabine 1,000 mg/m(2) twice daily day 1 through 14, every 3 weeks). The primary study end point was objective response rate (ORR).
  
  
  RESULTS
  In the intention-to-treat patient population (n = 177), ORR was 46% (95% CI, 35 to 57) for CAPIRI plus cetuximab versus 48% (95% CI, 37 to 59) for CAPOX plus cetuximab. Analysis of the KRAS gene mutation status was performed in 81.4% of the intention to treat population. Patients with KRAS wild-type in the CAPIRI plus cetuximab arm showed an ORR of 50.0%, a PFS of 6.2 months and an OS of 21.1 months. In the CAPOX plus cetuximab arm, an ORR of 44.9%, a PFS of 7.1 months and an OS of 23.5 months were observed. While ORR and PFS were comparable in KRAS wild-type and mutant subgroups, a trend toward longer survival was associated with KRAS wild-type. Both regimens had manageable toxicity profiles and were safe.
  
  
  CONCLUSIONS
  This randomized trial demonstrates that the addition of cetuximab to CAPIRI or CAPOX is effective and safe in first-line treatment of mCRC. In the analyzed regimens, ORR and PFS did not differ according to KRAS gene mutation status.
authors.affiliation: University of Munich, Klinikum Muenchen-Grosshadern, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Moosmann
authors.forename: Ludwig Fischer
authors.initials: LF
authors.lastname: von Weikersthal
authors.forename: Ursula
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.forename: Martina
authors.initials: M
authors.lastname: Stauch
authors.forename: Holger G
authors.initials: HG
authors.lastname: Hass
authors.forename: Herrmann
authors.initials: H
authors.lastname: Dietzfelbinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Oruzio
authors.forename: Stefan
authors.initials: S
authors.lastname: Klein
authors.forename: Klaus
authors.initials: K
authors.lastname: Zellmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.forename: Mathias
authors.initials: M
authors.lastname: Schulze
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Abenhardt
authors.forename: Gerhard
authors.initials: G
authors.lastname: Puchtler
authors.forename: Herbert
authors.initials: H
authors.lastname: Kappauf
authors.forename: Johann
authors.initials: J
authors.lastname: Mittermüller
authors.forename: Christopher
authors.initials: C
authors.lastname: Haberl
authors.forename: Andreas
authors.initials: A
authors.lastname: Schalhorn
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005858:Germany; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin