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Xeroderma pigmentosum group D haplotype predicts for response, survival, and toxicity after platinum-based chemotherapy in advanced nonsmall cell lung cancer.
Booton, Richard Ward, Timothy H Heighway, Jim Taylor, Pat Power, Fiona Ashcroft, Linda Morris, Julie Thatcher, Nick
Booton, Richard
Ward, Timothy H
Heighway, Jim
Taylor, Pat
Power, Fiona
Ashcroft, Linda
Morris, Julie
Thatcher, Nick
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Abstract
BACKGROUND: The treatment of lung cancer has reached a therapeutic plateau. Several mechanisms of platinum resistance have been described, including the removal of platinum-DNA adduct by nucleotide excision repair (NER). Polymorphisms within the Xeroderma pigmentosum Group D protein (XPD), a member of the NER pathway, are associated with alterations in enzyme activity and may change sensitivity to platinum-based chemotherapy. The authors investigated the relation between XPD polymorphisms and treatment response, toxicity, and overall survival in patients who received platinum-based chemotherapy for advanced nonsmall cell lung cancer (NSCLC). METHODS: Between 2001 and 2002, 108 patients with chemotherapy-naive, advanced NSCLC were recruited. Associations between XPD312/751 polymorphisms and XPD haplotype and treatment response, toxicity. and survival were evaluated. RESULTS: Significant correlations were observed between XPD haplotype and Grade 4 neutropenia and overall survival together with a greater response to platinum-based chemotherapy for the XPD *A haplotype. CONCLUSIONS: The XPD haplotype may represent a useful pharmacogenomic marker of platinum-based chemotherapy in patients with advanced NSCLC and requires prospective validation.
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Date
2006-06-01
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cncr.21885.pdf
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Keywords
Lung Cancer
Type
Article
Citation
Xeroderma pigmentosum group D haplotype predicts for response, survival, and toxicity after platinum-based chemotherapy in advanced nonsmall cell lung cancer. 2006, 106 (11):2421-7 Cancer