title: Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer: a multicenter study in Japan.
abstract: OBJECTIVE
  This retrospective study evaluated the treatment outcomes and clinical relevance of the KRAS mutation status in Japanese metastatic colorectal cancer patients treated with second-line and later cetuximab-containing therapy.
  
  
  METHODS
  The subjects comprised 65 patients with metastatic colorectal cancer who received cetuximab-containing therapy. At the start of cetuximab-containing therapy, the KRAS mutation status had been proven to be wild type in 12 patients. Tumors were retrospectively screened for KRAS mutations using direct sequencing.
  
  
  RESULTS
  A detailed analysis revealed the presence of 24 wild-type (57.1 %) and 18 mutant tumors (42.9 %). Grade 3-4 neutropenia and anemia were observed in 21 (32.3 %) and nine (13.8 %) patients, respectively. An acne-like rash was observed in 50 patients (76.9 %), and among them three patients (4.6 %) experienced a Grade 3 rash. A KRAS mutation was associated with resistance to cetuximab-containing treatment (11.1 vs. 41.7 % responders among 18 mutant and 36 wild-type patients, respectively; P = 0.03). A KRAS mutation was also associated with poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients, respectively; P = 0.018).
  
  
  CONCLUSIONS
  The present results indicated the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan, h-saeki@surg2.med.kyushu-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Emi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kumashiro
authors.forename: Hajime
authors.initials: H
authors.lastname: Otsu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawano
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ida
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kimura
authors.forename: Eriko
authors.initials: E
authors.lastname: Tokunaga
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Shimokawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab