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Leo A.D.,Dell | Jerusalem G.,University of Liege | Petruzelka L.,Charles University | Torres R.,Instituto Nacional Del Cancer | And 11 more authors.
Journal of the National Cancer Institute

BackgroundAt the time of the initial analysis of overall survival (OS) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) randomized, double-blind, phase III trial, approximately 50% of patients had died. A final analysis of OS was subsequently planned for when 75% of patients had died.MethodsPatients were randomly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 (±3) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections (one fulvestrant and one placebo [identical in appearance to study drug]) on days 0, 14 (two placebo injections only), and 28 and every 28 (±3) days thereafter. OS was analyzed using an unadjusted log-rank test. No adjustments were made for multiplicity. Serious adverse events (SAEs) and best response to subsequent therapy were also reported. All statistical tests were two-sided.ResultsIn total, 736 women (median age = 61.0 years) were randomly assigned to fulvestrant 500mg (n = 362) or 250mg (n = 374). At the final survival analysis, 554 of 736 (75.3%) patients had died. Median OS was 26.4 months for fulvestrant 500mg and 22.3 months for 250mg (hazard ratio = 0.81; 95% confidence interval = 0.69-0.96; nominal P =. 02). There were no clinically important differences in SAE profiles between the treatment groups; no clustering of SAEs could be detected in either treatment group. Type of first subsequent therapy and objective responses to first subsequent therapy were well balanced between the two treatment groups.ConclusionsIn patients with locally advanced or metastatic estrogen receptor-positive breast cancer, fulvestrant 500mg is associated with a 19% reduction in risk of death and a 4.1-month difference in median OS compared with fulvestrant 250mg. Fulvestrant 500mg was well tolerated, and no new safety concerns were identified. © 2013 © The Author 2013. Published by Oxford University Press. Source

Santibanez M.,University of the Frontier | Diaz A.,Instituto Nacional Del Cancer | Figueroa R.G.,University of the Frontier
X-Ray Spectrometry

When obtaining a chemical element image through energy dispersive X-ray fluorescence (EDXRF) scanning of a specific sample, it is important to determine the minimum detection time (MDT) required per dot (pixel) and per element in order to identify the minority and the trace elements present in the sample. Starting from the statistical criteria of limit of detection, quantitative estimations can be made regarding the concentration of elements present in the samples, determining the MDT which fits to the limit of detection previously established. Given that with this technique it is possible to implement in vivo applications, in this work, a process was developed for the MDT that is capable of generating the minimum radiation exposure in imaging EDXRF. For this proposal, the MDT is determined for metals, such as Fe, Cu, and Pb, given their great biomedical interest, in a series of equivalent bone and soft tissue phantom samples. Consequently, a criteria for global scanning time per dot was established, hence providing an elemental XRF image according to the As Low As Reasonably Achievable principles, i.e. as low an exposure as reasonably possible for each sample type studied by this sort of devices, in order to obtain appropriate information for each field of application. © 2016 John Wiley & Sons, Ltd. Source

Figueroa R.G.,University of the Frontier | Lozano E.,Instituto Nacional Del Cancer | Flores M.A.,University of the Frontier
International Journal of Morphology

The knowledge of the concentration and spatial distribution that chemical elements present in different organs and tissues is a useful parameter for diagnosis of certain diseases or element levels above limits accepted as healthy. Therefore, development of techniques to identify the chemical elements present in a living tissue and obtaining information about their concentration and spatial distribution might be relevant to determine an individual's health status. This work presents an application of a new X-ray fluorescence technique, energy dispersive by scanning, which can be applied to samples of different composition and shape, unlike most of the existing techniques, only applicable to flat samples. This technique allows the acquisition of two-dimensional images of the chemical elements present in a sample in both mono and multielemental mode. In this work the technique is applied to a set of human bone samples and tarsus and fingers of a dead Gallus gallus (chicken), obtaining a 2D spatial distribution with different levels of fluorescence intensity, depending on the detected element and its concentration. The acquired images consider areas up to 104 mm2, with a spatial resolution of 400 mm2 and an acquisition time of about 20 min. Calculations of the radiation dose associated with this type of XRF analysis were also carried out, and the findings show that the levels applied to obtain an XRF image are tolerable. The latter leads to the conclusion that it would be possible to use this technique for an in vivo application. Source

Tannock I.F.,Princess Margaret Cancer Center | Fizazi K.,University Paris - Sud | Karlsson C.T.,Onkologiska Kliniken Norrlands Universitetssjukhus | Flechon A.,CRLC Leon Berard | And 16 more authors.
The Lancet Oncology

Background: Docetaxel plus prednisone is standard first-line chemotherapy for men with metastatic castrate-resistant prostate cancer. Aflibercept is a recombinant human fusion protein that binds A and B isoforms of VEGF and placental growth factor, thereby inhibiting angiogenesis. We assessed whether the addition of aflibercept to docetaxel and prednisone would improve overall survival in men with metastatic castrate-resistant prostate cancer compared with the addition of placebo to docetaxel and prednisone. Methods: VENICE was a phase 3, multicentre, randomised double-blind placebo-controlled parallel group study done in 31 countries (187 sites). Men with metastatic castrate-resistant prostate cancer, adequate organ function, and no prior chemotherapy were treated with docetaxel (75 mg/m2 intravenously every 3 weeks) and oral prednisone (5 mg twice daily) and randomly allocated (1:1) to receive aflibercept (6 mg/kg) or placebo, intravenously, every 3 weeks. Treatment allocation was done centrally via an interactive voice response system, using a computer-generated sequence with a permuted-block size of four and stratified according Eastern Co-operative Group performance status (0-1 vs 2). Patients, investigators, and other individuals responsible for study conduct and data analysis were masked to treatment assignment. Aflibercept or placebo vials were supplied in identical boxes. The primary endpoint was overall survival using intention-to-treat analysis. This is the primary analysis of the completed trial. The study is registered with ClinicalTrials.gov, number NCT00519285. Findings: Between Aug 17, 2007, and Feb 11, 2010, 1224 men were randomly allocated to treatment: 612 to each group. At final analysis, median follow-up was 35 months (IQR 29-41) and 873 men had died. Median overall survival was 22·1 months (95·6% CI 20·3-24·1) in the aflibercept group and 21·2 months (19·6-23·8) in the placebo group (stratified hazard ratio 0·94, 95·6% CI 0·82-1·08; p=0·38). We recorded a higher incidence of grade 3-4 gastrointestinal disorders (182 [30%] vs 48 [8·0%]), haemorrhagic events (32 [5·2%] vs ten [1·7%]), hypertension (81 [13%] vs 20 [3·3%]), fatigue (97 [16%] vs 46 [7·7%]), infections (123 [20%] vs 60 [10%]) and treatment-related fatal adverse events (21 [3·4%] vs nine [1·5%]) in the aflibercept group than in the placebo group. Interpretation: Aflibercept in combination with docetaxel and prednisone given as first-line chemotherapy for men with metastatic castrate-resistant prostate cancer resulted in no improvement in overall survival and added toxicity compared with placebo. Docetaxel plus prednisone remains the standard treatment for such men who need first-line chemotherapy. Funding: Sanofi and Regeneron Pharmaceuticals Inc. © 2013 Elsevier Ltd. Source

Figueroa R.G.,University of the Frontier | Lozano E.,Instituto Nacional Del Cancer | Bongiovannic G.,CONICET
Revista Mexicana de Fisica

Visualization of elemental distributions of biological tissue is gaining importance in many disciplines of biological, forensic, and medical research. Furthermore, the maps of elements have wide application in archeology for the understanding of the pigments, modes of preservation and environmental context. Since major advances in relation to collimators and detectors have yielded micro scale images, the chemical mapping via synchrotron scanning micro-X-ray fluorescence spectrometry (SR-μXRF) is widely used as microanalytical techniques. However, the acquisition time is a limitation of current SR-μXRF imaging protocols, doing tedious micro analysis of samples of more than 1 cm and very difficult to study of larger samples such as animal organ, whole organisms, work of art, etc. Recently we have developed a robotic system to image the chemistry of large specimens rapidly at concentration levels of parts per million. Multiple images of distribution of elements can be obtained on surfaces of 100×100 mm and a spatial resolution of up to 0.2 mm2 per pixel, with a spectral capture time up to 1 ms per point. This system has proven to be highly efficient for the XRF mapping of elements in large biological samples, achieving comparables results to those obtained by SR-μXRF. Thus, images of As and Cu accumulation in renal cortex of arsenic-exposed rats were obtained by both methodologies. However, the new imaging system enables the XRF scanning in few minutes, whereas SR-μXRF required several hours. These and other advantages as well as the potential applications of this system, will be discussed. Source

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