Disease-free survival of patients after surgical resection of non-small cell lung carcinoma and correlation with excision repair cross-complementation group 1 expression and genotype.

BACKGROUND AND OBJECTIVE: Expression of excision repair cross-complementation group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who have undergone surgical resection of non-small cell lung cancer (NSCLC). However, in patients treated with adjuvant chemotherapy after surgical resection, ERCC1 correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to be a predictive marker of the efficacy of treatment with taxanes or vinorelbine. METHODS: Tumour tissues (n = 363) from patients with surgically resected NSCLC were analysed retrospectively. Tissue sections were labelled with ERCC1- and TUBB3-specific antibodies. Using genomic DNA from 262 patients, single nucleotide polymorphisms of the ERCC1 gene (T19007C and C8092A) were genotyped by PCR-restriction fragment length polymorphism analysis. RESULTS: Only 5.9% of patients with stage I disease (14/238) and 61.6% of patients with stages II-III disease (77/125) received adjuvant chemotherapy. Relapses were noted in 30.6% (111) of patients, and among these, 31 ultimately succumbed. The relapse rate (RR) was 24.8% for stage I disease, and 41.6% for stages II-III disease. The RR was significantly lower in ERCC1-positive (24.3%) as compared with ERCC1-negative patients (36.3%, P = 0.014) and was lower in patients with the AA/CA genotype at the ERCC1 C8092A locus (29.5%) compared with those with the CC genotype (42.1%, P = 0.034). The median disease-free survival (DFS) time was 62.3 months. DFS was significantly greater in ERCC1-positive patients (62.3 months) than in ERCC1-negative patients (48.0 months, P = 0.042). In a multivariate analysis, ERCC1 expression and the C8092A polymorphism were independent prognostic factors in patients with stage I disease who were naïve to chemotherapy. CONCLUSIONS: ERCC1 expression and the AA/CA genotype at the C8092A locus were correlated with a good prognosis in patients who had undergone surgical resection of NSCLC.

Investigating Effective Combinations of Anti-cancer Drugs and Radiation Therapy for Treating Non-small Cell Lung Cancer with Using Two Cell Lines

PURPOSE: Radiotherapy had been used for treating unresectable locally advanced non-small cell lung cancer (NSCLC). However, the survival rate after radiotherapy alone is low and this primarily due to the failure of local disease control and distant metastasis. For achieving better disease control, radiotherapy has recently been combined with chemotherapy in various ways. In this study, we aimed to find the most effective combination of chemotherapy and radiotherapy for treating NSCLC. MATERIALS AND METHODS: Two human lung cancer cell lines (NCI-H520 and A549) and various chemotherapeutic agents (paclitaxel, docetaxel, gemcitabine and cisplatin) were used for this study. The radiation doses were 0, 2, 4 and 8 Gy. After processing various combinations according to the radiation doses and the concentrations of thechemotherapeutic agents, cell survival was quantified by MTT (3-(4,5-Dimethylhiazol- 2-yl)-2,5-diphenyltetrazoliumbromide) assay. For the evaluation of synergism between chemotherapy and radiotherapy, we used a combination index that as calculated by Chou and Talalay's method and with using Calcusyn software. RESULTS: Among the various combinations of chemotherapeutic agents and radiation doses, concurrent chemoradiation therapy (CCRT) led to the highest apoptosis rate and it showed frequent synergism. When taxane was administrated as a chemotherapeutic agent, chemotherapy followed by radiotherapy was the most effective combination. When high-dose chemotherapeutic agents were added to CCRT, induction chemotherapy resulted in a higher apoptosis rate and more frequent synergism than did consolidation chemotherapy. CONCLUSION: When radiotherapy is combined with chemotherapy for treating the NCI-H520 and A549 cell lines, CCRT is the most effective combination. If a high-dose chemotherapeutic agent is added to CCRT, then induction chemotherapy is more effective than consolidation chemotherapy.