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dc.contributor.authorBooton, Richard
dc.contributor.authorWard, Timothy H
dc.contributor.authorAshcroft, Linda
dc.contributor.authorMorris, Julie
dc.contributor.authorHeighway, Jim
dc.contributor.authorThatcher, Nick
dc.date.accessioned2009-07-07T16:27:44Z
dc.date.available2009-07-07T16:27:44Z
dc.date.issued2007-10
dc.identifier.citationERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer. 2007, 2 (10):902-6 J Thorac Oncolen
dc.identifier.issn1556-1380
dc.identifier.pmid17909351
dc.identifier.doi10.1097/JTO.0b013e318155a637
dc.identifier.urihttp://hdl.handle.net/10541/72884
dc.description.abstractBACKGROUND: Platinum-based therapy is pivotal to the treatment of advanced non-small cell lung Cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. We sought to determine the influence of ERCC1 mRNA expression in advanced NSCLC on chemotherapy response, toxicity, and survival after platinum-based chemotherapy. METHODS: Patients randomized to a phase III trial of platinum-based chemotherapy were eligible for inclusion. Formalin-fixed paraffin-embedded tumor biopsies were retrieved for mRNA extraction and purification before quantitative real-time polymerase chain reaction analysis using Taqman technology. Expression data were correlated with treatment response, toxicity, and overall survival. RESULTS: Sixty-six patients were enrolled. No statistically significant relationship existed between ERCC1 mRNA expression and response to chemotherapy (p = 0.794) or hematological toxicity. No statistically significant difference in median survival was demonstrated according to ERCC1 expression (high expression, 415 days, 95% confidence interval [95%CI]: 197-633 days; low expression, 327 days [95%CI: 211-433 days]; p = 0.801). High ERCC1 mRNA expression was associated with a hazard ratio for death of 0.96 (95% CI 0.919-1.004; p = 0.08). CONCLUSION: In contrast to recent publications, ERCC1 mRNA expression in our study did not favor a prognostically better outcome after platinum-based chemotherapy in advanced NSCLC. We explore potential reasons for this, including the need for cautious interpretation of mRNA expression data from archival materials and highlight the need for additional translational research linking gene expression with a promising ERCC1 polymorphism.
dc.language.isoenen
dc.subjectSquamous Cell Canceren
dc.subjectLung Canceren
dc.subjectCancer Stagingen
dc.subject.meshAdenocarcinoma
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshCarboplatin
dc.subject.meshCarcinoma, Large Cell
dc.subject.meshCarcinoma, Non-Small-Cell Lung
dc.subject.meshChemotherapy, Adjuvant
dc.subject.meshCisplatin
dc.subject.meshDNA Repair
dc.subject.meshDNA-Binding Proteins
dc.subject.meshEndonucleases
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshIfosfamide
dc.subject.meshLung Neoplasms
dc.subject.meshMale
dc.subject.meshMitomycin
dc.subject.meshNeoplasm Staging
dc.subject.meshNeoplasms, Squamous Cell
dc.subject.meshPolymorphism, Genetic
dc.subject.meshRNA, Messenger
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshSurvival Rate
dc.subject.meshTaxoids
dc.subject.meshTreatment Outcome
dc.titleERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentChristie Hospital NHS Trust & Paterson Institute for Cancer Research, Manchester, United Kingdom. r.booton@btopenworld.comen
dc.identifier.journalJournal of Thoracic Oncologyen
html.description.abstractBACKGROUND: Platinum-based therapy is pivotal to the treatment of advanced non-small cell lung Cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. We sought to determine the influence of ERCC1 mRNA expression in advanced NSCLC on chemotherapy response, toxicity, and survival after platinum-based chemotherapy. METHODS: Patients randomized to a phase III trial of platinum-based chemotherapy were eligible for inclusion. Formalin-fixed paraffin-embedded tumor biopsies were retrieved for mRNA extraction and purification before quantitative real-time polymerase chain reaction analysis using Taqman technology. Expression data were correlated with treatment response, toxicity, and overall survival. RESULTS: Sixty-six patients were enrolled. No statistically significant relationship existed between ERCC1 mRNA expression and response to chemotherapy (p = 0.794) or hematological toxicity. No statistically significant difference in median survival was demonstrated according to ERCC1 expression (high expression, 415 days, 95% confidence interval [95%CI]: 197-633 days; low expression, 327 days [95%CI: 211-433 days]; p = 0.801). High ERCC1 mRNA expression was associated with a hazard ratio for death of 0.96 (95% CI 0.919-1.004; p = 0.08). CONCLUSION: In contrast to recent publications, ERCC1 mRNA expression in our study did not favor a prognostically better outcome after platinum-based chemotherapy in advanced NSCLC. We explore potential reasons for this, including the need for cautious interpretation of mRNA expression data from archival materials and highlight the need for additional translational research linking gene expression with a promising ERCC1 polymorphism.


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