1,720,962 research outputs found
Abstract 4062: A computational driven protocol of metronomic oral vinorelbine in metastatic non small cell lung cancer
No full textAbstract
Over the last decade, metronomic chemotherapy (MC) has emerged as an alternative way to administrate chemotherapy. MC can be defined as regular administration of low/less-toxic doses without extended drug-free breaks. Because countless schedules are possible, testing them empirically looks like an unachievable goal. Therefore, mathematical modeling can be an effective tool to determine appropriate metronomic strategies.
A phase Ia/Ib study based on a mathematical model of oral vinorelbine in metastatic NSCLC and malignant pleural mesothelioma was designed to confirm safety and evaluate efficacy of a new metronomic regimen (Elharrar et al. 2016). The optimized schedule providing weekly Day1 (D1), D2 and D4 with respective doses of 60, 30 and 60 mg was suggested by in silico simulations using a Pharmacokinetic-Pharmacodynamic (PKPD) model taking into account vinorelbine PK, PD toxicities and PD efficacy (Faivre et al. 2013). Trial recruitment will be two-staged, as 12 patients have been enrolled to confirm safety and consolidate the calibration of model parameters. An extension phase on 20-extra patients will be conducted to evaluate the efficacy of the optimized protocol. Monolix 4.3.3 was used for population PKPD analysis.
A three-compartment model best described oral vinorelbine PK data. PK analysis revealed a high inter-individual variability on drug exposure (CV=73%). PD toxicity (neutropenia) was adequately described by a modified Friberg model (Friberg et al. 2002), considering continuous administrations of metronomic dosing regimen. On the 12 recruited patients, 3 (25%) presented either a stable disease (SD) or a partial response (PR). No direct link has been established between toxicity (grade 4 neutropenia) and drug exposure. However, responders to treatment were those presenting a higher vinorelbine area under the curve (p=0.02). Tumor assessments were used to adjust efficacy parameters. The model was used to simulate alternative metronomic scenarios targeting higher efficacy with similar toxicity. Simulations showed that the initial proposed schedule was the most appropriate in terms of efficacy/toxicity balance. Its efficacy will be evaluated in the second part of the study.
This trial can be considered as a proof-of-concept study demonstrating the feasibility to run a computational-driven protocol to ensure an optimal efficacy/toxicity balance in cancer patients.
Citation Format: Diane-Charlotte Imbs, Raouf El Cheikh, Joseph Ciccolini, Raphaël Serre, Fabrice Barlesi, Dominique Barbolosi. A computational driven protocol of metronomic oral vinorelbine in metastatic non small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4062. doi:10.1158/1538-7445.AM2017-4062</jats:p
Abstract 4529: Optimization of the sequence for the administration of bevacizumab in combination with pemetrexed and cisplatin in NSCLC : a pharmacology based in vivo study
No full textAbstract
Introduction: Bevacizumab is active in advanced non-small cell lung cancer (NSCLC) and is administred in combination with chemotherapy in first line for non squamous NSCLC. However the best sequence of administration has not been defined. Previously published data suggest that before acting as an antiangiogenic drug, Bevacizumab would initially and transitory normalized the vascularization of the tumor. This initial phase could be thus be optimal to administrate chemotherapy. By using mathematic modeling, we showed that sequential administration of chemotherapy 3 days after Bevacizumab may be more beneficial than concomitant administration. Herein we tested and compared concomitant versus different schema of sequential administration of Bevacizumb with chemotherapy in NSCLC.
Methods: H460 Luc + cells were transfected with dTomato allowing to measure tumor growth by fluorescence. Nude mice were engrafted subcutaneously with around 120,000 cells. Fluorescence was used to monitor tumor growth twice a week and treated with Bevacizumab, Cisplatin and Pemetrexed with various sequences of administration. A total of 15-16 replicates were included in each therapeutic group.
Results Five therapeutic schema were compared : 1) Cisplatine-Pemetrexed only ; 2) concomitant administration of Bevacizumab with Cisplatine-Pemetrexed ; 3) chemotherapy 3 days after Bevacizumab predicted to be the optimal sequence by mathematic modeling; 4) chemotherapy 8 days after Bevacizumab predicted to be the worse sequence by mathematic modeling; 5) control group receiving placebo. Tumor growth was reduced of 38% in group 3 as compared with group 2, but this difference remains non significant (p=0.13), but was significantly reduced compared to groups 1, 4 and 5. The median survival was the longest in group 3 (74 days), as compared with group 2 (70 days), group 4 (67 days), group 1 (54 days) and control group (40 days).
Conclusion: This in vivo study indicate that the sequential administration of Bevacizumab three days before chemotherapy in NSCLC may be the optimal schema as compared with concomitant administration or longer delay as predicted by mathematic modeling. Mechanistic and pharmacokinetic analyses as well as biomarker studies are currently ongoing and should be shortly available.
Citation Format: arnaud boyer, diane-charlotte imbs, raouf el cheikh, celine mascaux, fabrice barlesi, dominique barbolosi, sebastien benzekry, joseph ciccolini. Optimization of the sequence for the administration of bevacizumab in combination with pemetrexed and cisplatin in NSCLC : a pharmacology based in vivo study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4529. doi:10.1158/1538-7445.AM2017-4529</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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