title: Phase II trial of cetuximab plus irinotecan for oxaliplatin- and irinotecan-based chemotherapy-refractory patients with advanced and/or metastatic colorectal cancer: evaluation of efficacy and safety based on KRAS mutation status (T-CORE0801).
abstract: BACKGROUND
  Mutations in the KRAS gene have been identified as negative predictors of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy by patients with metastatic colorectal cancer (mCRC). However, it has been based on the study of mainly Caucasian mCRC patients. This prospective study investigated the relationship between the mutation status of EGFR-related genes including KRAS and the response rate (RR) to cetuximab plus irinotecan therapy in Japanese mCRC patients.
  
  
  METHODS
  Samples taken from 43 chemotherapy-refractory mCRC patients who had undergone cetuximab plus irinotecan therapy at 11 medical centers in Japan were subjected to direct DNA sequencing to determine the KRAS, BRAF, PIK3CA, NRAS, and AKT1 mutation status. The clinical outcome after the treatment was evaluated for each mutation status.
  
  
  RESULTS
  KRAS mutations were detected in 31.7% of 41 eligible patients. The RR to cetuximab plus irinotecan therapy was found to be 17.9 and 0% in the KRAS wild-type and mutant subgroups, respectively.
  
  
  CONCLUSIONS
  Despite the identification of a lower-than-expected RR to treatment by the KRAS wild-type subgroup, KRAS mutation status appears to be a useful predictive marker of response to cetuximab plus irinotecan therapy in Japanese mCRC patients.
authors: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors: Hiroshi
authors: H
authors: Soeda
authors: Hideki
authors: H
authors: Shimodaira
authors: Makio
authors: M
authors: Gamoh
authors: Hideaki
authors: H
authors: Ando
authors: Hideki
authors: H
authors: Isobe
authors: Takeshi
authors: T
authors: Suto
authors: Shin
authors: S
authors: Takahashi
authors: Yuichi
authors: Y
authors: Kakudo
authors: Kenji
authors: K
authors: Amagai
authors: Takahiro
authors: T
authors: Mori
authors: Mika
authors: M
authors: Watanabe
authors: Takuhiro
authors: T
authors: Yamaguchi
authors: Shunsuke
authors: S
authors: Kato
authors: Chikashi
authors: C
authors: Ishioka
mesh_terms: 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*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / 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; D008565:Membrane Proteins; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D000077146:Irinotecan; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin