1. Randomized Phase 3 Trial of Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer
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Miguel, Martín, Alvaro, Rodríguez-Lescure, Amparo, Ruiz, Emilio, Alba, Lourdes, Calvo, Manuel, Ruiz-Borrego, Blanca, Munárriz, César A, Rodríguez, Carmen, Crespo, Enrique, de Alava, José Antonio, López García-Asenjo, María Dolores, Guitián, Sergio, Almenar, Jesús Fernando, González-Palacios, Francisco, Vera, José, Palacios, Manuel, Ramos, Jose Manuel, Gracia Marco, Ana, Lluch, Isabel, Alvarez, Miguel Angel, Seguí, José Ignacio, Mayordomo, Antonio, Antón, José Manuel, Baena, Arrate, Plazaola, Alfonso, Modolell, Amadeu, Pelegrí, Jose Ramón, Mel, Enrique, Aranda, Encarna, Adrover, José Valero, Alvarez, José Luis, García Puche, Pedro, Sánchez-Rovira, Sonia, Gonzalez, José Manuel, López-Vega, M Francisca, Garijo, GEICAM 9906 Study Investigators, [Martín,M] Department of Medical Oncology, Hospital Universitario San Carlos, Madrid, Spain. [López García-Asenjo,JA] Department of Pathology, Hospital Universitario San Carlos, Madrid, Spain. [Rodríguez-Lescure,A] Department of Medical Oncology, Hospital Universitario de Elche, Spain. [Ruiz,A] Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain. [Almenar,S] Department of Pathology, Instituto Valenciano de Oncologia, Valencia, Spain. [Alba Conejo,E] Department of Medical Oncology, Hospital Virgen de la Victoria, Málaga, Spain. [Calvo,L] Department of Medical Oncology, Complejo Hospitalario Juan Canalejo, La Coruña, Spain. [Guitián,MD] Department of Pathology, Complejo Hospitalario Juan Canalejo, La Coruña, Spain. [Ruiz-Borrego,M] Department of Medical Oncology, Hospital Vírgen del Rocío, Sevilla, Spain [Palacios,J] Department of Pathology, Hospital Vírgen del Rocío, Sevilla, Spain. [Muñárriz,B] Department of Medical Oncology, Hospital La Fe, Valencia, Spain. [Vera,F] Department of Pathology, Hospital La Fe, Valencia, Spain. [Rodríguez, CA] Department of Medical Oncology, Hospital Universitario de Salamanca, Salamanca, Spain. [Crespo,C] Department of Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain. [González-Palacios,JF] Department of Pathology, Hospital Ramón y Cajal, Madrid, Spain. [de Álava,E] Department of Pathology, Centro de Investigación del Cáncer, Salamanca, Spain. [Ramos,M] Department of Medical Oncology, Centro Oncológico de Galicia, La Coruña, Spain. [Gracia Marco,JM] Department of Medical Oncology, Hospital de Cabueñes, Gijón, Spain. [Lluch,A] Department of Medical Oncology, Hospital Clínico Universitario de Valencia, Valencia, Spain. [Álvarez,I] Department of Medical Oncology, Hospital de Donostia, San Sebastián, Spain. [Seguí,MA] Department of Medical Oncology, Hospital Parc Taulí, Sabadell, Spain. [Mayordomo,JI] Department of Medical Oncology, Hospital Clínico Lozano Blesa, Zaragoza, Spain. [Antón,A] Department of Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain. [Baena,JM] Department of Medical Oncology, Complejo Hospitalario Puerta del Mar, Cádiz, Spain. [Plazaola,A] Department of Medical Oncology, Instituto Oncológico de Guipúzcoa, San Sebastián, Spain. [Modolell,A] Department of Medical Oncology, Clínica Corachan, Barcelona, Spain. [Pelegrí,A] Department of Medical Oncology, Hospital Universitario San Joan de Reus, Tarragona, Spain. [Mel,JR] Department of Medical Oncology, Complejo Hospitalario Xeral Calde, Lugo, Spain. [Aranda,E] Department of Medical Oncology, Hospital Provincial de Córdoba, Córdoba, Spain. [Adrover,E] Department of Medical Oncology, Hospital General de Alicante, Alicante, Spain. [Valero Álvarez,J] Hospital Provincial de Zamora, Spain. [García Puche,JL] Department of Medical Oncology, Hospital San Cecilio de Granada, Granada, Spain. [Sánchez-Rovira,P] Department of Medical Oncology, Hospital Ciudad de Jaén, Jaén, Spain. [González,S] Department of Medical Oncology, Mutua de Terrasa, Terrasa, Spain. [López-Vega,JM] Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain., and Department of Medical Oncology, Hospital Ciudad de Jaén, Jaén, Spain
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Oncology ,medicine.medical_treatment ,Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Supervivencia sin Enfermedad ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2 [Medical Subject Headings] ,Antineoplastic Combined Chemotherapy Protocols ,Estimación de Kaplan-Meier ,Receptor erbB-2 ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Schedule [Medical Subject Headings] ,Hazard ratio ,Pronóstico ,Epirrubicina ,Prognosis ,Immunohistochemistry ,Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Ductal::Carcinoma, Ductal, Breast [Medical Subject Headings] ,Receptors, Estrogen ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Neoplasm Staging [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Biological Markers::Tumor Markers, Biological [Medical Subject Headings] ,Receptors, Progesterone ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Alicyclic::Cycloparaffins::Cyclodecanes::Taxoids::Paclitaxel [Medical Subject Headings] ,medicine.medical_specialty ,Paclitaxel ,Fluorouracilo ,Axillary lymph nodes ,Resultado del Tratamiento ,Anciano ,Disease-Free Survival ,Drug Administration Schedule ,Breast cancer ,Carcinoma Lobular ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,Adjuvant therapy ,Humans ,Cyclophosphamide ,Aged ,ERBB2 protein, human ,medicine.disease ,Carcinoma, Lobular ,Check Tags::Female [Medical Subject Headings] ,Modelos de Riesgos Proporcionales ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytological Preparation Techniques::Staining and Labeling::In Situ Hybridization::In Situ Hybridization, Fluorescence [Medical Subject Headings] ,Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Survival Analysis::Disease-Free Survival [Medical Subject Headings] ,Cancer Research ,Receptor, ErbB-2 ,Kaplan-Meier Estimate ,Antineoplásicos Fitogénicos ,Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Lobular [Medical Subject Headings] ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil [Medical Subject Headings] ,Infusions, Intravenous ,In Situ Hybridization, Fluorescence ,Carcinoma, Ductal, Breast ,Neoplasias de la Mama ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings] ,Middle Aged ,Chemotherapy regimen ,Treatment Outcome ,medicine.anatomical_structure ,Female ,Fluorouracil ,Breast disease ,Infusiones Intravenosas ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Phytogenic [Medical Subject Headings] ,Epirubicin ,medicine.drug ,Adult ,Protocolos de Quimioterapia Combinada Antineoplásica ,Hibridación Fluorescente In Situ ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Halogenated::Mustard Compounds::Nitrogen Mustard Compounds::Phosphoramide Mustards::Cyclophosphamide [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings] ,Breast Neoplasms ,Ciclofosfamida ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Proportional Hazards Models [Medical Subject Headings] ,Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Immunochemistry [Medical Subject Headings] ,Predictive Value of Tests ,Internal medicine ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthacenes::Anthracyclines::Daunorubicin::Doxorubicin::Epirubicin [Medical Subject Headings] ,Biomarkers, Tumor ,medicine ,Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings] ,Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings] ,Neoplasm Staging ,Proportional Hazards Models ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,Receptores de Progesterona ,Chemotherapy ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Kaplan-Meier Estimate [Medical Subject Headings] ,business.industry ,Esquema de Medicación ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Infusions, Parenteral::Infusions, Intravenous [Medical Subject Headings] ,Antineoplastic Agents, Phytogenic ,Estadificación de Neoplasias ,Receptores Estrogénicos ,Surgery ,Marcadores Biológicos de Tumor ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings] ,business ,Carcinoma Ductal de Mama ,Inmunohistoquímica - Abstract
Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy. Yes
- Published
- 2008
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