ABSTRACT
Objective: Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations have higher response rate and more prolonged survival following treatment with single-agent EGFR tyrosine kinase inhibitor (EGFR-TKI) compared with patients with wild-type EGFR. However, all patients treated with reversible inhibitors develop acquired re-sistance over time. The mechanisms of resistance are complicated. The lack of established therapeutic options for patients after a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. This study evaluates the in-fluence of EGFR-TKI retreatment following chemotherapy after failure of initial EGFR-TKI within at least six months on NSCLC pa-tients. Methods:The data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. After chemotherapy, the patients were retreated with EGFR-TKI (gefitinib 250 mg qd or erlotinib 150 mg qd), and the tumor progression was observed. The patients were assessed for adverse events and response to therapy. Targeted tumor lesions were as-sessed with CT scan. Results:Of the 27 patients who received EGFR–TKI retreatment, 1 (3.7%) patient was observed in complete re-sponse (CR), 8 (29.6%) patients in partial response (PR), 14 (51.9%) patients in stable disease (SD), and 4 (14.8%) patients in progres-sive disease (PD). The disease control rate (DCR) was 85.2%(95%CI=62%-94%). The median progression-free survival (mPFS) was 6 months (95%CI=1-29). Of the 13 patients who received the same EGFR-TKI, 1 patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were observed. The DCR was 84.6%, and the mPFS was 5 months. Of the 14 patients who received another EG-FR-TKI, 0 patient in CR, 6 patients in PR, 6 patients in SD, and 2 patients in PD were observed. The DCR was 85.7%, and the mPFS was 9.5 months. Significant difference was found between the 2 groups in progression-free survival but not in response rate or disease control rate. Conclusion:Retreatment of EGFR-TKIs can be considered an option after failure of chemotherapy for patients who were previously controlled by EGFR-TKI treatment.
ABSTRACT
Background and purpose:The incidence of hepatoma is high. The outcome of treatment on hepatoma is poor.So we investigated the effect and mechanism of a selective cyclooxygenase-2 inhibitor celecoxib on the proliferation and apoptosis of SMMC-7721 hepatoma cell line. Methods:MTT assay was used to study the inhibitive effect of celecoxib on the growth of SMMC-7721 hepatoma cell. The effect of celecoxib on cell cycle and apoptosis on cells was studied by flow cytometry(FCM).Transmission electron microscopy (TEM) was used to display the morphological change of the SMMC-7721 hepatoma cell . The biochemical character of apoptosis was viewed on the agarose gel electrophoresis.The expression of bax gene and bcl-2 gene were measured by immunohistochemistry.Results:The SMMC-7721 cells were cultured in media that contained 25,50,75,100 ?mol/L celecoxib,by means of MTT, the inhibition rate was(15?3)%,(34.6?2.4)%,56.8?1.0)%,(86.2?0.4)% respectively after 24 hours; but the inhibition rate was (33.4?0.7)%,(66.7?1.8)%,(76.1?2.4)%,(97.3?0.8)% respectively after 48 hours(P