Prospective analysis of KRAS wild-type patients with metastatic colorectal cancer using cetuximab plus FOLFIRI or FOLFOX4 treatment regimens

Genet Mol Res. 2011 Oct 3;10(4):3002-12. doi: 10.4238/2011.October.3.4.

Abstract

Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, has proven to be efficient in the treatment of metastatic colorectal cancer. We made a prospective study of the efficacy and toxicities of cetuximab-combination first-line (FOLFOX4) versus second/third-line (FOLFIRI) chemotherapy in 98 KRAS wild-type patients who had metastatic colorectal cancer. Wild-type KRAS had been identified by direct sequencing. Associations between clinical response/progression-free survival/overall survival/toxicities and cetuximab-combination chemotherapy timing were evaluated. The overall response rate was significantly higher for first-line treatment than for second/third-line treatment (relative risk = 1.707, 95% confidence interval = 1.121-2.598). Both progression-free survival and overall survival indicated significantly longer survival of first-line treatment than second/third-line treatment patients. This study is a validation of a molecular analysis of KRAS wild-type status for the prediction of response to cetuximab-combination chemotherapy for metastatic colorectal cancer patients; its predictive role was less prominent in the second/third-line than in the first-line treatment patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Drug Administration Routes
  • Drug Administration Schedule
  • Drug-Related Side Effects and Adverse Reactions
  • ErbB Receptors / antagonists & inhibitors
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Mutation
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use
  • Prospective Studies
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • KRAS protein, human
  • Organoplatinum Compounds
  • Proto-Oncogene Proteins
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol