Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

A síndrome metabólica é transtorno complexo, caracterizada por conjunto de fatores de risco cardiovasculares, relacionados com resistência à insulina e obesidade abdominal. A obesidade provoca alterações no metabolismo da glicose em vários tecidos, o que promove hiperinsulinemia -apesar de também haver outros mecanismos reduzidos na reciclagem hepática de insulina. Atualmente, estima-se que 24% da população adulta dos EUA e entre 50 e 60% na população acima de 50 anos possuem essa síndrome e algumas projeções indicam que, em 2010, os EUA terão de 50 a 75 milhões de pessoas afetadas 3,4,14,16 . Por proposta feita pela Organização Mundial de Saúde, define-se síndrome metabólica quando o indivíduo possuir dois ou mais dos seguintes componentes 5,7: 1) glicemia de jejum > 125 mg/dL, glicemia aleatória > 200 mg/dL ou com um TOTG > 200 mg/dL ou 140 -200 mg/dL com sintomas clássicos de hiperglicemia; 2) pressão arterial elevada (>130/>85 mmHg); 3) triglicerídeos plasmáticos elevados (> 1,7 mmol -150mg/dL); 4) colesterol HDL baixo (< 40 para homens e < 50 para mulheres); 5) obesidade central (relação cintura/quadril > 0,9 para homens e > 0,8 para mulheres) e/ou índice de massa corpórea (IMC) acima de 30 Kg/m²; 6) microalbuminúria >15 µg/min ou relação albumina/creatinina urinária >30 mg.Outros componentes estudados nesta síndrome também foram relacionados com a resistência à insulina e/ou tendem a agrupar-se com a síndrome principal, entre eles: hiperuricemia, proporção aumentada de LDL pequena e densa, aumento da concentração de lipoproteínas remanescentes, distúrbios da coagulação e da fibrinólise (elevação do fibrinogênio), disfunção endotelial, inflamação da parede arterial, angina microvascular e síndrome de ovários policísticos 14,18 . Outros grupos de especialistas apresentaram outras versões para a definição da síndrome (três itens ou mais), como o Programa Nacional de Educação em Colesterol

10748 Background: Nab-P improves outcomes when compared against single agent cremophor-based P, as does the addition of bevacizumab or gemcitabine to the same agent. There are no available data regarding combinations of Nab-P with B and/or G. Ongoing investigational efforts are evaluating various doublets with these agents, but, to the best of our knowledge, not all 3 of them in the same regimen. All drugs are currently FDA-approved in the treatment of breast cancer. Methods: Review of single-institution experience, evaluating safety and preliminary evidence of activity with the use of Nab-P and B with and without G in heavily pretreated her2neu negative metastatic breast cancer patients. Assessment of response was undertaken by the investigators independently of treating physician. RECIST criteria were used. Three patients received Nab-P and B at the following doses: Nab-P 100 mg/m2, B 10 mg/kg every 2 weeks, and 2 patients received all 3 drugs as follows: Nab-P 100 mg/m2, G 1,000 mg/m2, B 10 mg/kg every 2 weeks. Results: Five women have been evaluated. Median age was 51 (range 34–69). Two patients had hormone-receptor positive disease and 3 had ER/PR/Her2neu-negative cancer. Prior number of regimens was 3 (range 2–7). Four patients had been treated with a taxane. One received both paclitaxel and docetaxel, and 3 docetaxel only. A median of 5 cycles have been administered (range 3–9). First-cycle grade 3/4 toxicity was seen in only one patient who had a baseline grade 2 thrombocytopenia that progressed to grade 3. The thrombocytopenia resolved without requiring transfusion and without any hemorrhagic complication. Another patient developed grade 2 peripheral neuropathy. Two patients are not yet assessable for response. At time of first evaluation 1 patient had progressive disease (Nab-P, B; 7 prior lines of treatment), one had stable disease (Nab-P, B, G; 3 prior lines of therapy, including docetaxel), and 1 had a partial response (Nab-P, B, G; 2 prior therapies, including docetaxel). Conclusions: These very preliminary data suggest that Nab-P in combination with B with and without G is a safe regimen and formal Phase I/II trials are being developed to confirm its clinical activity. [Table: see text]

complete response in 5% and progressive disease in 8%. Of the subjects undergoing chemotherapy (n¼102), 33 experienced grade 3 or 4 AE and 14 subjects had to discontinue chemotherapy before 4 cycles. ECOG PS improved to 0/1 in 22 (19.6%) subjects who underwent any form of treatment. The median survival of the study cohort was 250 days. On a multivariate analysis, the presence of brain metastases was associated with poor OS (HR [95% CI] 7.6 [1.4-41.6]) Conclusion: Most of the Elderly patients with NSCLC and poor PS had an advanced stage at presentation. Majority tolerate chemotherapy well and some have an improvement in their PS. The presence of brain metastases is associated with a poor survival.

Abstract:Currently, multiple lines of cytotoxic chemotherapy for treatment of metastatic breast cancer are available, and Taxanes, used as monotherapy or in combination with anti-angiogenic drugs, such as Bevacizumab, are one of the most used schemes in clinical practice. These drugs have different side effects and the liver is one of the most affected organs. The objective of this paper is to report three cases of metastatic breast cancer with positive expression of hormone receptors and without amplification of HER-2 protein that were treated with Taxane and Bevacizumab, developed pseudocirrosis probably caused by these drugs and died due to liver failure. It can be drawn from the study that liver failure, as a pseudocirrhosis evolution, is an unusual but lethal event that may occur during the treatment of metastatic breast cancer with Taxanes and Bevacizumab. This warns the importance of diagnostic suspicion of this pathology.