106 research outputs found
Emerging treatments and combinations in the management of NSCLC: clinical potential of nintedanib
Martin Reck,1 Anders Mellemgaard2 1Department of Thoracic Oncology, Lung Clinic Grosshansdorf, and member of the Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 2Department of Oncology, Herlev University Hospital, Copenhagen, Denmark Abstract: There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy. Keywords: nintedanib, non-small cell lung cancer, second-line treatment, docetaxel, adenocarcinoma, antiangiogenesi
Læsø Land:Økologi og kultur i et øsamfund 1550-1900
udgivelse af afdøde prof. em. Bjarne Stoklunds værk om Læsøs historie som produkt af en serie tilpasniner til økologiske, økonomiske, demografisk og politiske forhold i perioden
Combination chemotherapy for treatment of metastasing non-small-cell lung carcinoma. Monotherapy of combinations of two or three agents--a survey of a Cochrane review
Udgivelsesdato: 2009-Ju
A modified exercise protocol may promote continuance of exercise after the intervention in lung cancer patients—a pragmatic uncontrolled trial
ERCC1 and Ki67 in Small Cell Lung Carcinoma and Other Neuroendocrine Tumors of the Lung: Distribution and Impact on Survival
BackgroundExcision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair mechanism. Ki67 is associated with the clinical course of several malignancies. The associations of ERCC1 and Ki67, clinical features and survival in small cell lung carcinoma (SCLC), typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LCNEC) were determined.Materials and MethodsWe included a consecutive series of 186 patients with SCLC treated with platinum-based chemotherapy and surgically treated patients with TC (n = 48), AC (n = 15) and LCNEC (n = 27). ERCC1 and Ki 67 were measured by immunohistochemistry and scored using published criteria.ResultsThe expression of ERCC1 was different among the different tumor types (p < 0.001). For patient with limited disease as well as extensive disease SCLC, no association of ERCC1 expression with survival was observed (p = 0.59). However, only 10% of SCLC tumors expressed ERCC1. For TC and AC, ERCC1 positive patients had better survival than ERCC1 negative patients. ERCC1 had no prognostic impact for LCNEC. A difference of the percentage of Ki67 LI was observed for the different tumor types (p < 0.001). The difference between TC and AC was significant (p = 0.02), as was the difference between low grade (TC+AC) and high grade NE (LCNEC + SCLC) (p < 0.001). For all included patients, a correlation between Ki67 and ERCC1 was observed (RSquare = 0.19, p < 0.001).ConclusionERCC1 expression in SCLC treated with platinum-based chemotherapy has no impact on survival. High expression of ERCC1 in TC might represent a clue to the failure of platinum-based therapy in these patients. ERCC1 expression has prognostic impact in lung carcinoids. Ki 67 might be considered as a supplementary test to the histopatologic classification of NE tumors
Medical treatment of lung cancer
Lung cancer causes most cancer-related deaths in the western world. In Denmark, over 4,700 cases of lung cancer are diagnosed annually. The medical treatment of lung cancer has undergone a significant development over the past 20 years. Adjuvant chemotherapy is given to some patients after surgery, and patients with inoperable, non-metastatic disease can be treated with combinations of chemotherapy and radiation therapy. The large group of patients with metastatic disease can be offered different forms of medical treatment as chemotherapy, targeted treatment or immunotherapy.</p
High specificity but low sensitivity of mutation-specific antibodies against EGFR mutations in non-small-cell lung cancer
Determination of epidermal growth factor receptor (EGFR) mutations has a pivotal impact on treatment of non-small-cell lung cancer (NSCLC). A standardized test has not yet been approved. So far, Sanger DNA sequencing has been widely used. Its rather low sensitivity has led to the development of more sensitive methods including real-time PCR (RT-PCR). Immunohistochemistry with mutation-specific antibodies might be a promising detection method. We evaluated 210 samples with NSCLC from an unselected Caucasian population. Extracted DNA was analyzed for EGFR mutations by RT-PCR (Therascreen EGFR PCR kit, Qiagen, UK; reference method). For immunohistochemistry, antibodies against exon19 deletions (clone 6B6), exon21 mutations (clone 43B2) from Cell Signaling Technology (Boston, USA) and EGFR variantIII (clone 218C9) from Dako (Copenhagen, DK) were applied. Protein expression was evaluated, and staining score (multipum of intensity (graded 0-3) and percentages (0-100%) of stained tumor cells) was calculated. Positivity was defined as staining score >0. Specificity of exon19 antibody was 98.8% (95% confidence interval=95.9-99.9%) and of exon21 antibody 97.8% (95% confidence interval=94.4-99.4%). Sensitivity of exon19 antibody was 63.2% (95% confidence interval=38.4-83.7%) and of exon21 antibody was 80.0% (95% confidence interval=44.4-97.5%). Seven exon19 and four exon21 mutations were false negatives (immunohistochemistry negative, RT-PCR positive). Two exon19 and three exon21 mutations were false positive (immunohistochemistry positive, RT-PCR negative). One false positive exon21 mutation had staining score 300. The EGFR variantIII antibody showed no correlation to EGFR mutation status determined by RT-PCR or to EGFR immunohistochemistry. High specificity of the mutation-specific antibodies was demonstrated. However, sensitivity was low, especially for exon19 deletions, and thus these antibodies cannot yet be used as screening method for EGFR mutations in NSCLC. Refinement of sensitivity for the mutation-specific antibodies is warranted to improve molecular diagnosis using EGFR immunohistochemistry.</p
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