ERCC1 Predicts a Poorer Platinum-based Chemotherapy Outcome but a Better Outcome for Uracil-Tegafur in the Resected Stage I-II NSCLC

BACKGROUND: The role of excision repair cross-complementation group 1 (ERCC1) has been controversial in non-small cell lung cancer (NSCLC) patients who received adjuvant chemotherapy with a platinum agent. We investigated ERCC1 expression in stage I-II NSCLC to clarify its significance for adjuvant chemotherapy. METHODS: The ERCC1 expression profile was evaluated by immunohistochemistry and compared according to adjuvant chemotherapeutic agents in 146 patients who underwent surgical resection for stage I-II NSCLC. The patients were divided into 3 groups; adjuvant chemotherapy with a platinum based agent (18.5%, 27/146); adjuvant chemotherapy with uracil-tegafur (UFT) (40.4%, 59/146); surgery-alone (41.1%, 60/146). RESULTS: Nuclear ERCC1 expression was detected in 71.9% (105/146) of NSCLC and was significantly associated with a shortened survival period in the group 1 patients who received the platinum based regimen after surgery. The group 2 patients who received UFT showed the longest survival period, followed by the surgery-alone group (overall survival, p=0.049; disease-free survival [DFS], p<0.001). CONCLUSIONS: These results suggest that stage I-II NSCLC patients with ERCC1 expression experience a shorter DFS period with adjuvant chemotherapy with a platinum based regimen and may benefit from adjuvant chemotherapy with UFT, instead of platinum after surgery.

An Analysis of HER-2/neu, ERCC1, and GST-pi in Advanced Non-Small Cell Lung Cancer Patients Who are Treated with Platinum-based Chemotherapy

BACKGROUND: Platinum-based chemotherapy has shown to be an effective first-line treatment for patients with advanced stage, unresectable non-small cell lung cancer (NSCLC). We evaluated the response rate to combination chemotherapy with cisplatin and taxane, and the significance of the HER-2/neu, ERCC1, and GST-pi status as predictive markers for the tumor response. METHODS: The HER-2/neu, ERCC1, and GST-pi status were analyzed in the biopsy specimens obtained from 35 patients with advanced stage NSCLC prior to cisplatin plus either paclitaxel or docetaxel chemotherapy. RESULTS: The response rate of the tumors to combination chemotherapy was 62.9% (22/35). HER-2/neu was amplified in 51.4% (18/35) of the tumors, and this was observed exclusively in patients with progressive disease (p=0.014). ERCC1 was overexpressed in 77.2% of the specimens (27/35), and this showed a tendency to correlate with the tumor response (p=0.057). GST-pi was detected in 85.7% of the specimens (30/35). Seventy-seven percent of the patients with a negative HER-2/neu and positive ERCC1 status showed a partial response, which was in contrast to only a 25% response rate for the patients with a positive HER-2/neu and negative ERCC1 status (p=0.006). The overall survival was prolonged in the patients without HER-2/neu amplification (15 vs 8.5 months, respectively, p=0.008). On multivariate analysis, the HER-2/neu status remained the significant predictor of survival (p=0.005). CONCLUSIONS: A combination of the ERCC1, HER-2/neu status may define a subset of patients with the most favorable response to combination chemotherapy regimens for treating advanced NSCLC.

Association between excision repair cross-complementation group 1 polymorphism and clinical outcome of platinum-based chemotherapy in patients with epithelial ovarian cancer

ERCC1 is a DNA repair gene and has been associated with resistance to DNA damaging agents. In this study we hypothesized that a polymorphism of ERCC1 Asn118Asn (C->T) might affect the platinum-resistance of epithelial ovarian cancer patients to platinum-taxane chemotherapy administered postoperatively. Using the SNapShot assay, we assessed this polymorphism in ERCC1 in 60 ovarian cancer patients. Platinum-resistance was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. Although not significant, platinum-resistance was less frequently observed in patients with the C/T+T/T genotype (P=0.064). Multivariate analysis showed that the C/T+T/T genotypes constituted an independent predictive factor of reduced risk of platinum-resistance in ovarian cancer (odds ratio 0.17, 95% confidence interval 0.04-0.74, P=0.018, Fisher's exact test). No significant correlation was observed between overall survival and the ERCC1 polymorphism. Our results suggest that genotyping of the ERCC1 polymorphism Asn118Asn may be useful for predicting the platinum-resistance of epithelial ovarian cancer patients. However, these findings require prospective confirmation.