Lung-Tumor Test Predicts Chemotherapy Outcome

Testing non-small-cell lung tumors for the presence of an enzyme that aids in DNA repair may predict whether patients will benefit from platinum-based chemotherapy.

The presence or absence of the DNA-repair enzyme, excision repair cross-complementing complementation group 1 (ERCC1), in non-small-cell lung tumors can predict which patients may have a survival benefit from a Platinol (cisplatin)-based adjuvant chemotherapy regimen.

In a study reported in the September 7, 2006, issue of the New England Journal of Medicine, Ken A. Olaussen, Ph.D., of the University of Paris (Paris, France), and colleagues used immunohistochemical analysis to determine the expression of the ERCC1 protein in 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 pathologic factors.

Patients whose tumors did not carry ERCC1 had better odds for survival--about 14 months longer--if they underwent chemotherpy. Five years after treatment, 47% of those who received chemotherapy were still alive. The five-year survival rate was 39% among those who did not undergo chemotherapy. Chemotherapy did not affect the survival of patients whose tumors carried ERCC1. However, among patients who did not get chemotherapy, ERCC1-positive patients survived longer than ERCC1-negative patients.

"ERCC1 is the limiting factor in nucleotide excision repair, which removes platinum-DNA adducts,” the authors wrote. "ERCC1 may also be involved in the repair of DNA double-strand breaks, especially those induced by interstrand cross-links. For this reason, the mechanism by which ERCC1 contributes to cisplatin resistance probably involves more than nucleotide excision repair. It is possible that the presence of ERCC1 reflects an inherent biologic characteristic of the tumor.”

The scientists concluded that 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.



Related Links:
University of Paris