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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / therapeutic use*
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Antibodies, Monoclonal, Humanized
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Camptothecin / administration & dosage
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Camptothecin / analogs & derivatives
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Camptothecin / therapeutic use
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Cetuximab
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / genetics
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Colorectal Neoplasms / mortality
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Colorectal Neoplasms / pathology
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DNA Mutational Analysis
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Disease-Free Survival
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Drug Administration Routes
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Drug Administration Schedule
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Drug-Related Side Effects and Adverse Reactions
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ErbB Receptors / antagonists & inhibitors
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Female
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Fluorouracil / administration & dosage
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Fluorouracil / therapeutic use
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Humans
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Leucovorin / administration & dosage
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Leucovorin / therapeutic use
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / genetics
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Liver Neoplasms / mortality
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Liver Neoplasms / secondary
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / genetics
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Lung Neoplasms / mortality
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Lung Neoplasms / secondary
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Male
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Middle Aged
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Mutation
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Organoplatinum Compounds / administration & dosage
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Organoplatinum Compounds / therapeutic use
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Prospective Studies
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins p21(ras)
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ras Proteins / genetics*
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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KRAS protein, human
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Organoplatinum Compounds
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Proto-Oncogene Proteins
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ErbB Receptors
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Proto-Oncogene Proteins p21(ras)
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ras Proteins
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Cetuximab
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Leucovorin
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Fluorouracil
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Camptothecin
Supplementary concepts
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Folfox protocol
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IFL protocol