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Genet Mol Res ; 10(4): 3002-12, 2011 Oct 03.
Article in English | MEDLINE | ID: mdl-21968808

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.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Cetuximab , 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/genetics , Liver Neoplasms/mortality , Liver Neoplasms/secondary , 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 p21(ras)
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