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Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer

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Abstract

Purpose

New therapeutic approaches are being developed based on findings that several genetic abnormalities underlying non-small-cell lung cancer (NSCLC) can influence chemosensitivity. The identification of molecular markers, useful for therapeutic decisions in lung cancer, is thus crucial for disease management. The present study evaluated single-nucleotide polymorphisms (SNPs) in XRCC3, XPD and Aurora kinase A in NSCLC patients in order to assess whether these biomarkers were able to predict the outcomes of the patients.

Methods

The Spanish Lung Cancer Group prospectively assessed this clinical study. Eligible patients had histologically confirmed stage IV or IIIB (with malignant pleural effusion) NSCLC, which had not previously been treated with chemotherapy, and a World Health Organization performance status (PS) of 0–1. Patients received intravenous doses of vinorelbine 25 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1, every 21 days for a maximum of 6 cycles. Venous blood was collected from each, and genomic DNA was isolated. SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 were assessed.

Results

The study included 180 patients. Median age was 62 years; 87 % were male; 34 % had PS 0; and 83 % had stage IV disease. The median number of cycles was 4. Time to progression was 5.1 months (95 % CI, 4.2–5.9). Overall median survival was 8.6 months (95 % CI, 7.1–10.1). There was no significant association between SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 in outcome or toxicity.

Conclusions

Our findings indicate that SNPs in XRCC3, XPD or Aurora kinase A cannot predict outcomes in advanced NSCLC patients treated with platinum-based chemotherapy.

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Acknowledgments

The authors thank the monitors, nurses, other support staff and the patients participating in the study. They also thank Francisco Javier Pérez for the statistical analysis. The authors also wish to thank Martin Hadley-Adams for assisting with the English language and preparing the manuscript.

Author information

Authors and Affiliations

  1. Servicio de Oncología Médica, Hospital Universitario Puerta de Hierro, Calle Manuel de Falla, 1, 28222, Majadahonda, Madrid, Spain

    M. Provencio & A. Sanchez

  2. Hospital General Universitario de Valencia, Valencia, Spain

    C. Camps

  3. Hospital Universitario Carlos Haya, Málaga, Spain

    M. Cobo

  4. Hospital Provincial de Castellon, Castellon, Spain

    R. De las Peñas

  5. Hospital Universitario General de Alicante, Alicante, Spain

    B. Massuti

  6. Hospital de Terrasa, Barcelona, Spain

    R. Blanco

  7. Hospital Universitario Arnau de Vilanova, Valencia, Spain

    V. Alberola

  8. Hospital Universitario La Princesa, Madrid, Spain

    U. Jimenez

  9. Hospital Universitario Virgen de las Nieves, Granada, Spain

    J. R. Delgado

  10. Catalan Institute of Oncology, Hospital Duran i Reynals, L’Hospitalet, Barcelona, Spain

    F. Cardenal

  11. Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

    M. Tarón, J. L. Ramírez & R. Rosell

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  1. M. Provencio
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  2. C. Camps
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  6. R. Blanco
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  7. V. Alberola
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  8. U. Jimenez
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  11. M. Tarón
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  12. J. L. Ramírez
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  13. A. Sanchez
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  14. R. Rosell
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Corresponding author

Correspondence to A. Sanchez.

Additional information

This study was carried out on behalf of the Spanish Lung Cancer Group.

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Provencio, M., Camps, C., Cobo, M. et al. Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer. Cancer Chemother Pharmacol 70, 883–890 (2012). https://doi.org/10.1007/s00280-012-1985-9

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  • DOI: https://doi.org/10.1007/s00280-012-1985-9

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