Olaussen KA et al. (2006) DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355: 983–991

The International Adjuvant Lung Cancer Trial (IALT) demonstrated improved survival with adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC). Although cisplatin-based chemotherapy is effective in some patients, however, it is associated with serious adverse events and is not always well tolerated. In vitro studies of the DNA excision repair protein ERCC1 have shown its expression to correlate with resistance to platinum compounds; thus, data on the expression of this protein in tumors might predict survival benefit from cisplatin-based chemotherapy. Patients from the IALT with completely resected NSCLC were enrolled into the IALT Biology study to investigate this outcome.

Immunohistochemistry was used to detect the ERCC1 protein in NSCLC specimens obtained during excision surgery. Among patients whose tumors lacked ERCC1 expression, those who underwent adjuvant chemotherapy with a cisplatin-based regimen lived significantly longer than did those who received no therapy (P = 0.002). This survival benefit was not seen for patients with ERCC1-positive tumors—indeed, a trend was observed for patients with ERCC1-positive tumors to perform better without chemotherapy. Among patients who did not receive adjuvant chemotherapy in the original study, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors (P = 0.009).

The authors conclude that patients with NSCLC who have ERCC1-negative tumors derive a benefit from adjuvant cisplatin-based chemotherapy whereas patients with ERCC1-positive tumors do not, and that ERCC1 protein expression is an independent predictor of the effectiveness of adjuvant chemotherapy.