A multicentre phase II gene expression profiling study of putative relationships between tumour biomarkers and clinical response with erlotinib in non-small-cell lung cancer
Tan, E.H. (National Cancer Centre (Singapur). Department of Medical Oncology)
Ramlau, R. (Regional Lung Disease Centre (Poznan). Department of Oncology)
Pluzanska, A. (Regional Oncology Centre (Lodz, Polònia). Oncological Chemotherapy Clinic)
Kuo, H. -P. (Chang Gung Memorial Hospital (Linkou, Taiwan). Department of Thoracic Medicine)
Reck, M. (Hospital Grosshansdorf (Grosshansdorf, Alemanya). Department of Thoracic Oncology)
Milanowski, J. (Akademia Medyczna w Lublinie (Lublin, Polònia). Department of Pneumology, Oncology and Allergology)
Au, J. S. -K. (Queen Elizabeth Hospital (Hong Kong). Department of Clinical Oncology)
Felip Font, Enriqueta (Hospitals Vall d'Hebron (Barcelona, Catalunya))
Yang, P. -C. (National Taiwan University Hospital (Taipei, Taiwan))
Damyanov, D. (Specialized Hospital for Active Treatment in Oncology (Sofia, Bulgaria))
Orlov, S. (Pavlov State Medical University. Research Institute of Pulmonology (Sant Petersburg, Rússia))
Akimov, M. (Hoffmann-La Roche (Basel, Suïssa))
Delmar, P. (Hoffmann-La Roche (Basel, Suïssa))
Essioux, L. (Hoffmann-La Roche (Basel, Suïssa))
Hillenbach, C. (Hoffmann-La Roche (Basel, Suïssa))
Klughammer, B. (Hoffmann-La Roche (Basel, Suïssa))
McLoughlin, P. (Hoffmann-La Roche (Basel, Suïssa))
Baselga Torres, Josep, 1959-, (Vall d'Hebron Hospitals)

Fecha: 2010
Resumen: Background: Identification of appropriate markers for predicting clinical benefit with erlotinib in non-small-cell lung cancer (NSCLC) may be able to guide patient selection for treatment. This open-label, multicentre, phase II trial aimed to identify genes with potential use as biomarkers for clinical benefit from erlotinib therapy. Methods: Adults with stage IIIb/IV NSCLC in whom one or more chemotherapy regimen had failed were treated with erlotinib (150 mg/day). Tumour biopsies were analysed using gene expression profiling with Affymetrix GeneChip_microarrays. Differentially expressed genes were verified using quantitative RT-PCR (qRT-PCR). Results: A total of 264 patients were enrolled in the study. Gene expression profiles found no statistically significant differentially expressed genes between patients with and without clinical benefit. In an exploratory analysis in responding versus nonresponding patients, three genes on chromosome 7 were expressed at higher levels in the responding group [epidermal growth factor receptor (EGFR), phosphoserine phosphatase (PSPH) and Rap guanine nucleotide exchange factor 5 (RAPGEF5)]. Independent quantification using qRT-PCR validated the association between EGFR and PSPH overexpression, but not RAPGEF5 overexpression, and clinical outcome. Conclusions: This study supports the use of erlotinib as an alternative to chemotherapy for patients with relapsed advanced NSCLC. Genetic amplification of the EGFR region of chromosome 7 may be associated with response to erlotinib therapy.
Derechos: Aquest document està subjecte a una llicència d'ús de Creative Commons, amb la qual es permet copiar, distribuir i comunicar públicament l'obra sempre que se'n citin l'autor original i la universitat i no se'n faci cap ús comercial ni obra derivada, tal com queda estipulat en la llicència d'ús Creative Commons
Lengua: Anglès
Documento: article ; publishedVersion
Materia: Biomarkers ; Epidermal growth factor receptor ; Gene expression ; Non-small-cell lung cancer ; PCR
Publicado en: Annals of oncology, Vol. 21, Issue 2 (2010) , p. 217-222, ISSN 1569-8041

PMID: 20110292

6 p, 263.8 KB

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