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Annals of Oncology 15:1194-1203, 2004
© 2004 European Society for Medical Oncology

Single nucleotide polymorphisms and outcome in docetaxel–cisplatin-treated advanced non-small-cell lung cancer

Background: Platinum-based doublets are the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). Excision-repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) are essential to the repair of cisplatin DNA adducts. Multidrug resistance 1 (MDR1) has been related to antimicrotubule resistance. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, XPD, RRM1 and MDR1, and ERCC1 mRNA expression, predicted survival in docetaxel–cisplatin-treated stage IV NSCLC patients.

Patients and methods: Using the TaqMan 5' nuclease assay, we examined ERCC1 118, XPD 751 and 312, RRM1 –37C/A, and MDR1 C3435T SNPs in peripheral blood lymphocytes (PBLs) obtained from 62 docetaxel–cisplatin-treated advanced NSCLC patients. ERCC1 expression was measured in RNA isolated from PBLs using real-time reverse transcriptase PCR.

Results: Overall median survival was 10.26 months. Median survival was 9.67 months for 34 patients with ERCC1 118 C/T, 9.74 months for 17 patients with T/T, and not reached for 11 patients with C/C (P=0.04). Similar significant differences in time to progression were observed according to ERCC1 118 genotype (P=0.03). No other significant differences were observed.

Conclusions: Patients homozygous for the ERCC1 118 C allele demonstrated a significantly better survival. ERCC1 SNP assessment could be an important component of tailored chemotherapy trials.

D. Isla1, C. Sarries2, R. Rosell2,*, G. Alonso3, M. Domine4, M. Taron2, G. Lopez-Vivanco5, C. Camps6, M. Botia2, L. Nuñez2, M. Sanchez-Ronco7, J. J. Sanchez7, M. Lopez-Brea8, I. Barneto9, A. Paredes10, B. Medina11, A. Artal12 and P. Lianes13 On behalf of the Spanish Lung Cancer Group{dagger}

1 Hospital Clinico Lozano Blesa, Zaragoza; 2 Institut Catala d'Oncologia, Hospital Germans Trias i Pujol, Barcelona; 3 Hospital Juan Canalejo, La Coruña; 4 Fundación Jimenez Diaz, Madrid; 5 Hospital de Cruces, Bilbao; 6 Hospital General de Valencia, Valencia; 7 Facultad de Medicina, Autonomous University of Madrid, Madrid; 8 Hospital Valdecilla, Santander; 9 Hospital Reina Sofia, Cordoba; 10 Hospital de Donostia, San Sebastian; 11 Hospital Ciudad de Jaen, Jaen; 12 Hospital Miguel Servet, Zaragoza; 13 Hospital de Mataro, Mataro, Spain

* Correspondence to: Dr R. Rosell, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Barcelona, Spain. Tel: +34-93-497-89-25; Fax: +34-93-497-89-50; Email: rrosell{at}ns.hugtip.scs.es

Key words: cisplatin, docetaxel, ERCC1, non-small-cell lung cancer, single nucleotide polymorphisms


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