title: [Analysis of the correlation with KRAS gene mutation status and the benefit of cetuximab plus irinotecan as third- line chemotherapy for the Treatment of unresectable metastatic colorectal cancer].
abstract: Mutation of the KRAS gene in patients with metastatic colorectal cancer(mCRC)has been established as a predictive marker of poor response to anti-EGFR cetuximab. The Japanese Society of Medical Oncology recommends that the KRAS mutation status at codon 12 and codon 13 should be genotyped by direct-sequencing or allele-specific PCR. In this study, we tested the point mutation of codon 12 and 13 in the KRAS gene by Luminex(xMAP)flow cytometry with sequence-specific oligonucleotide probes for 39 out of 64 unresectable mCRC patients enrolled from Sep 2008 to Oct 2009, who were administered cetuximab in combination with irinotecan(CPT-11)as third-line therapy. We retrospectively analyzed the relationship between KRAS mutation status and responses to combination therapy. Mutations in the KRAS gene were detected in 38. 5% of cases(codon12: 73%, codon 13: 27%), and the median follow-up time was 8. 2 months(range, 1. 4-15. 2 months). The response rates for patients with KRAS wild-type and patients with KRAS mutations were 33. 3%(95%CI 14. 5-52. 2%)and 0%(p=0. 015); the disease control rates were 75%(95%CI 57. 7-92. 3%)and 40%(95%CI, 15. 2-64. 8%; p=0. 044); the median TTF was 7 months(95%CI 4. 6-9. 3)and 2. 3 months(95%CI 1. 3-3. 2; p=0. 0007), and the median OS was 12. 9 months(95%CI 6. 7-19. 1)and 10. 8 months(95%CI 5. 0-16. 7; p=0. 15), respectively. Therefore, we concluded that the KRAS mutation in mCRC is a predictive factor for the lack of response to combination therapy with cetuximab plus CPT- 11, as reported in previous clinical studies.
authors.affiliation: The Cancer Institute Hospital of the Japanese Foundation For Cancer Research.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Asai
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinozaki
authors.forename: Akira
authors.initials: A
authors.lastname: Nozaki
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Watanabe
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Suenaga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matuzaka
authors.forename: Keisho
authors.initials: K
authors.lastname: Chin
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016879:Salvage Therapy; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin