DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy
Ken A Olaussen, Ariane Dunant, Pierre Fouret, Elisabeth Brambilla, Fabrice André, Vincent Haddad, Estelle Taranchon, Martin Filipits, Robert Pirker, Helmut H Popper, Rolf Stahel, Laure Sabatier, Jean-Pierre Pignon, Thomas Tursz, Thierry Le Chevalier, Jean-Charles Soria, IALT Bio Investigators, Ken A Olaussen, Ariane Dunant, Pierre Fouret, Elisabeth Brambilla, Fabrice André, Vincent Haddad, Estelle Taranchon, Martin Filipits, Robert Pirker, Helmut H Popper, Rolf Stahel, Laure Sabatier, Jean-Pierre Pignon, Thomas Tursz, Thierry Le Chevalier, Jean-Charles Soria, IALT Bio Investigators
Abstract
Background: Adjuvant cisplatin-based chemotherapy improves survival among patients with completely resected non-small-cell lung cancer, but there is no validated clinical or biologic predictor of the benefit of chemotherapy.
Methods: We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group 1 (ERCC1) protein in operative specimens of non-small-cell lung cancer. The patients had been enrolled in the International Adjuvant Lung Cancer Trial, thereby allowing a comparison of the effect of adjuvant cisplatin-based chemotherapy on survival, according to ERCC1 expression. Overall survival was analyzed with a Cox model adjusted for clinical and pathological factors.
Results: Among 761 tumors, ERCC1 expression was positive in 335 (44%) and negative in 426 (56%). A benefit from cisplatin-based adjuvant chemotherapy was associated with the absence of ERCC1 (test for interaction, P=0.009). Adjuvant chemotherapy, as compared with observation, significantly prolonged survival among patients with ERCC1-negative tumors (adjusted hazard ratio for death, 0.65; 95% confidence interval [CI], 0.50 to 0.86; P=0.002) but not among patients with ERCC1-positive tumors (adjusted hazard ratio for death, 1.14; 95% CI, 0.84 to 1.55; P=0.40). Among patients who did not receive adjuvant chemotherapy, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors (adjusted hazard ratio for death, 0.66; 95% CI, 0.49 to 0.90; P=0.009).
Conclusions: Patients with completely resected non-small-cell lung cancer and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors do not.
Copyright 2006 Massachusetts Medical Society.
Source: PubMed