Abstract
Background: The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1-3 gene polymorphisms on outcomes of patients was examined.Methods:Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.Results:Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036).Conclusion:This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy.
| Original language | English |
|---|---|
| Pages (from-to) | 1695-1703 |
| Number of pages | 9 |
| Journal | British Journal of Cancer |
| Volume | 108 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Apr 30 2013 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin. / Tiseo, M.; Bordi, P.; Bortesi, B.; Boni, L.; Boni, C.; Baldini, E.; Grossi, F.; Recchia, F.; Zanelli, F.; Fontanini, G.; Naldi, N.; Campanini, N.; Azzoni, C.; Bordi, C.; Ardizzoni, A.
In: British Journal of Cancer, Vol. 108, No. 8, 30.04.2013, p. 1695-1703.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin
AU - Tiseo, M.
AU - Bordi, P.
AU - Bortesi, B.
AU - Boni, L.
AU - Boni, C.
AU - Baldini, E.
AU - Grossi, F.
AU - Recchia, F.
AU - Zanelli, F.
AU - Fontanini, G.
AU - Naldi, N.
AU - Campanini, N.
AU - Azzoni, C.
AU - Bordi, C.
AU - Ardizzoni, A.
PY - 2013/4/30
Y1 - 2013/4/30
N2 - Background: The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1-3 gene polymorphisms on outcomes of patients was examined.Methods:Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.Results:Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036).Conclusion:This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy.
AB - Background: The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1-3 gene polymorphisms on outcomes of patients was examined.Methods:Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.Results:Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036).Conclusion:This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy.
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U2 - 10.1038/bjc.2013.127
DO - 10.1038/bjc.2013.127
M3 - Article
C2 - 23549037
AN - SCOPUS:84877064645
VL - 108
SP - 1695
EP - 1703
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 8
ER -