Pemetrexed in Previously Treated Non-small Cell Lung Cancer Patients with Poor Performance Status

Background and objective Pemetrexed have been approved for the treatment of patients affected by advanced non-small cell lung cancner(NSCLC) in progression after first-line chemotherapy.We evaluated the activity and feasibility of pemetrexed in previously treated NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC were evaluated from April 2007 to March 2009.The patients had relapsed or progressed after prior chemotherapy treatment.Pemetrexed(500 mg/m2) was administered intravenously once every 3 weeks after progression to prior chemotherapy.The tumor response was evaluated according to RECIST criteria by chest CT at every 2 cycles of chemotherapy.Results A total 61 patients were eligible for analysis.Performance status of them(100%) was over 2.The response rate and disease control rate were 14.7% and 37.7% respectively.Non-squamous cell carcinoma histology was significantly associated with a superior response rate(P=0.045) and disease control rate(P=0.008).The median survival time and the median progression free survival(PFS) time were 6.11 months and 2.17 months,respectively.Comparing the efficacy of pemetrexed in these two settings [second-line versus(12/61) more than third(49/61)],there was no significant difference in regard to median survival(11.18 months vs 11.46 months,P=0.922,5),but PFS was more longer in third-or further-line groups than second-line group(1.39 months vs 2.25 months,P=0.015,3).Conclusion Pemetrexed is a feasible regimen in previously treated NSCLC with poor performance status.

The Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Idiopathic Interstitisal Pneumonia

Background: Idiopathic interstitial pneumonia is characterized by fibroblast proliferation and extracellular matrix (ECM) accumulation. Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) have been shown to regulate remodeling of the ECM, which indicates that they are important factors in the process of lung fibrosis. Therefore, we evaluated the expression of MMPs and TIMPs in tissues obtained from patients with idiopathic interstitial pneumonia and control tissues. Methods: Thirty-seven patients who were diagnosed with IIP (22: IPF, 13: NSIP, 2: COP) and 5 controls were enrolled in this study. The MMP-2 and -9 activity in lung tissue obtained from these patients was analyzed using gelatin zymography and the levels of TIMP-1 and -2 were measured by western blotting. We also evaluated the expression of MMP-2 and -9, as well as that of TIMP-1 and -2 in lung tissue using immunohistochemistry. Results: The levels of MMP-2 and MMP-9 were significantly increased in patients with IPF compared to those with NSIP and COP. The activities of TIMP-1 and -2 were also higher in patients with IPF than NSIP/COP patients and control subjects. There were no significant differences observed in the activities of MMPs and TIMPs obtained from patients with NSIP/COP and control subjects. The immunohistochemical analysis showed that TIMP-2 and MMP-2 were strongly stained at the fibroblasts of the fibroblastic foci in patients with IPF. Conclusions: These results suggest that over-expression of gelatinases and TIMPs in patients with IPF are important factors in the irreversible fibrosis that is associated with lung parenchyma.