BACKGROUND: Pemetrexed, a multi-targeted antifolate has been used as a second line treatment against non-small cell lung cancer (NSCLC). We aimed to clarify the efficacy and survival according to line of treatment, histologic type, and expression of thymidylate synthase (TS). METHODS: Ninety-eight patients were treated with pemetrexed as a second line treatment (n=43) or as an additional course of treatment (n=55). TS expression was studied with immunohistochemistry and graded as 0 to 3 based on the extent of expression. RESULTS: The response rate (RR) in 98 subjects was 10.2% and the disease control rate (DCR=PR+SD) was 30.6%. RR and DCR were 12.7% and 32.7% in non-squamous cell carcinoma (NSQC) compared to 7.0% and 27.9% in squamous cell carcinoma (SQC) (p>.05). No significant differences in RR and DCR were observed between a second line group (4.7%, 20.9%) and a further line group (14.5%, 38.2%). A similar trend was observed in the 88 response evaluable subjects. TS was expressed in 28.6% (grade 1), 24.5% (grade 2) and 7.1% (grade 3), respectively, and it was not expressed in 39.8% of subjects. TS expression rate was significantly higher in the SQC (72.1%) compared to NSQC (50.9%, p=0.033). However, the efficacy of pemetrexed was not significantly different by the extent of TS expression. CONCLUSION: Pemetrexed showed efficacy, not only in a second-line setting, but also in further lines of treatment for NSCLC. The efficacy of pemetrexed tended to be higher in patients with NSQC compared to SQC. TS expression rate was significantly higher in SQC compared to NSQC.
Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Glutamates ; Guanine ; Humans ; Immunohistochemistry ; Thymidylate Synthase ; Pemetrexed

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.
Apoptosis ; Bridged Compounds ; Carcinoma, Non-Small-Cell Lung ; Cell Line ; Cell Survival ; Consolidation Chemotherapy ; Deoxycytidine ; Humans ; Induction Chemotherapy ; Lung Neoplasms ; Neoplasm Metastasis ; Survival Rate ; Taxoids