Comparative outcome assessment of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small-cell lung cancer: A network meta-analysis

Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced nonsmall- cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection. Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC. Cochrane guidelines were used for statistical analysis. Results: 3,179 patients were included. All EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR for gefitinib, erlotinib and afatinib were 52.1%, 67.3% and 61.6% respectively. HRs for PFS were 0.62 (95% CI, 0.38-1.00) for gefitinib, 0.28 (95% CI, 0.17-0.45) for erlotinib and 0.40 (95% CI, 0.20-0.83) for afatinib. HRs for OS were not statistically significant for any agent. Conclusions: Our results suggest similar clinical efficacy and higher toxicity of Afatinib treatment. As this still remains the agent with best CSF penetration, we suggest its use is limited to patients presenting with brain metastasis. We suggest the use of Gefitinib in patients without CNS involvement. Faced with the impossibility to dose-reduce Gefitinib, Erlotinib represents a tolerable and effective alternative to Afatinib and Gefitinib if response to EGFR inhibition is considered still effective.Logistic provision from the Cearense School of Oncology, Ceará Cancer Institute, Haroldo Juaçaba Hospital, Fortaleza, Ceará, Brazil, and The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral & Liverpool, England, United Kingdom. RAM has received honoraria from Pfizer Advisory Board, Zodiac advisory board, AstraZeneca, Novartis, National Science Centre, Krakow, Poland, and educational grant from Pierre Fabre, Amgem. RAM is ad hoc consultant at Ministry of Health, Brasília, Brazil. The other authors have no conflicts of interest in this manuscript. GM has received honoraria from Bristol Myers Squibb, Roche and AstraZeneca

Açaí clarificado por microfiltração.

bitstream/item/74942/1/pub-146.pd

On the growth of perturbations in interacting dark energy and dark matter fluids

The covariant generalizations of the background dark sector coupling suggested in G. Mangano, G. Miele and V. Pettorino, Mod. Phys. Lett. A 18, 831 (2003) are considered. The evolution of perturbations is studied with detailed attention to interaction rate that is proportional to the product of dark matter and dark energy densities. It is shown that some classes of models with coupling of this type do not suffer from early time instabilities in strong coupling regime.Comment: 11 pages, 2 figures. v3: minor changes, typos fixe

Neotectonic activity on the Carcavai fault zone (Algarve, Portugal)

Studies performed on the Carcavai fault zone, Eastern Algarve, revealed several deformational features in Plio-Quaternary sediments with potential neotectonic implications. These features include fracturing (faults and joints) and clastic dikes, located along the Carcavai fault. Most of the fractures appear to be the expression of the fault activity affecting the Plio-Quaternary sediments. This is suggested by a consistent strike, subparallel to the major tectonic structure, and by the location pattern. Evidences of the fault activity were also identified in the Mesozoic and Paleozoic rocks, though the age of that deformation is poorly constrained. It consists in the presence of zones of intensely brecciated rock and of adjoining coarse sedimentary deposits probably related to the dismantling of a fault scarp. The acquired data point to a late hercynian structure, reactivated as a left-lateral strike-slip fault with a thrust component during the Plio-Quaternary