Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: A multicenter randomized study by the Hellenic Oncology Research Group (HORG)
Mavroudis D.,University of Crete |
Saloustros E.,Oncology Unit |
Malamos N.,Elena Venizelou Hospital |
Kakolyris S.,University General Hospital of Alexandroupolis |
And 5 more authors.
Annals of Oncology | Year: 2015
Background: Adjuvant trastuzumab in combination with chemotherapy improves survival of women with HER2-positive early breast cancer. In this study, we compared 12 versus 6 months of adjuvant trastuzumab. Patients and methods: Axillary node-positive or high-risk node-negative women with HER2-positive early breast cancer were randomized to receive 12 or 6 months of adjuvant trastuzumab concurrently with dose-dense, granulocyte colony-stimulating factor (G-CSF)-supported docetaxel (75 mg/m2 every 14 days for four cycles). All patients received upfront dose-dense, G-CSF-supported FEC (5-fluorouracil 700 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 700 mg/m2 every 14 days for four cycles). Randomization was carried out before commence of chemotherapy. The primary end point was the 3-year disease-free survival (DFS). Results: A total of 481 patients were randomized to receive 12 months (n = 241) or 6 months (n = 240) of adjuvant trastuzumab. Chemotherapy was completed in 99% and 98% of patients, while trastuzumab therapy in 100% and 96% of patients in the 12- and 6-month groups, respectively. After 47 and 51 months of median follow-up, there were 17 (7.1%) and 28 (11.7%) disease relapses in the 12- and 6-month groups (P = 0.08). The 3-year DFS was 95.7% versus 93.3% in favor of the 12-month treatment group (hazard ratio = 1.57; 95% confidence interval 0.86-2.10; P = 0.137). There was no difference in terms of overall survival and cardiac toxicity between the two groups. Conclusions: Our study failed to show noninferiority for the 6-month arm. The results further support the current standard of care that is administration of adjuvant trastuzumab for 12 months. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Pagkalis S.,Democritus University of Thrace |
Mantadakis E.,Democritus University of Thrace |
Mavros M.N.,Alfa Institute of Biomedical science AIBS |
Ammari C.,University General Hospital of Alexandroupolis |
And 2 more authors.
Drugs | Year: 2011
Aminoglycosides constitute one of the oldest classes of antimicrobials. Despite their toxicity, mainly nephrotoxicity and ototoxicity, aminoglycosides are valuable in current clinical practice, since they retain good activity against multidrug-resistant Gram-negative pathogens, such as Pseudomonas aeruginosa and Acinetobacter spp. Time-kill studies have shown a concentration-dependent and partially concentration-dependent bacterial killing against Gram-negative and Gram-positive bacteria, respectively. Pharmacodynamic data gathered over recent decades show that the administration of aminoglycosides by an extended-interval dosing scheme takes advantage of the maximum potential of these agents, with the goal of achieving an area under the concentration-time curve (AUC) of 100mg·hL over 24 hours and a peak plasma drug concentration (C max) to minimum inhibitory concentration (MIC) ratio of 810. Several clinical conditions that are common in seriously ill patients result in expansion of the extracellular space and can lead to a lower than desirable C max with the usual loading dose. Extended-interval dosing schemes allow adequate time to decrease bacterial adaptive resistance, a phenomenon characterized by slow concentration-independent killing. Adaptive resistance is minimized by the complete clearance of the drug before the subsequent dose, thus favouring the extended-interval dosing schemes. The efficacy of these schemes is also safeguarded by the observed post-antibiotic sub-MIC effect and post-antibiotic leukocyte enhancement, which inhibit bacterial regrowth when the serum aminoglycoside levels fall below the MIC of the pathogen. In everyday clinical practice, aminoglycosides are usually used empirically to treat severe sepsis and septic shock while awaiting the results of antimicrobial susceptibility testing. The European Committee on Antimicrobial Susceptibility Testing acknowledges the regimen-dependent nature of clinical breakpoints for aminoglycosides, i.e. of MIC values that classify bacterial isolates into sensitive or resistant, and bases its recommendations on extended-interval dosing. To a large extent, the lack of correlation between in vitro antimicrobial susceptibility testing and clinical outcome is derived from the fact that the available clinical breakpoints for aminoglycosides are set based on mean pharmacokinetic parameters obtained in healthy volunteers and not sick patients. The nephrotoxicity associated with once-versus multiple-daily administration of aminoglycosides has been assessed in numerous prospective randomized trials and by several meta-analyses. The once-daily dosing schedule provides a longer time of administration until the threshold for nephrotoxicity is met. Regarding ototoxicity, no dosing regimen appears to be less ototoxic than another. Inactivation of aminoglycosides inside the bacterial pathogens occurs by diverse modifying enzymes and by operation of multidrug efflux systems, making both of these potential targets for inhibition. In summary, despite their use for several decades, the ideal method of administration and the preferred dosing schemes of aminoglycosides for most of their therapeutic indications need further refinement. Individualized pharmacodynamic monitoring has the potential of minimizing the toxicity and the clinical failures of these agents in critically ill patients. © 2011 Adis Data Information BV. All rights reserved.
Arvaniti A.,University General Hospital of Alexandroupolis
Psychiatrikē = Psychiatriki | Year: 2012
Recent studies indicate that the pregnancy rates of mothers with schizophrenia do not differ significantly from those of the general population. Mothers' severe mental illness, combined with poor social support and comorbidity, may significantly affect her parenting capacity. However, the poor quality of parenting by psychotic mothers should not be taken for granted, in advance. Some of them may become excellent parents while other may abuse their children and finally lose custody because of this. The parenting capacity is significantly influenced by the existing insight of patient-parent's disease. Assessing the parenting capacity comprises the measurement of insight and of the risk of child abuse as well. Factors associated with increased risk for child abuse are: (a) active psychiatric symptomatology, (b) history of violent behavior in the past, (c) maternal history of abuse during childhood, (d) dangerous domestic environment, (e) stressful events and poor social support to the mother and (f) unrealistic parental expectations. These factors should be assessed both clinically and by using the appropriate psychometric tools. Tools which have been widely used for this purpose are: (a) "Schedule for Assessment of Insight-SAI", (b) "Childhood Trauma Interview", (c) "Home Observation for the Measurement of the Environment Inventory-HOME" and "Home Screening Questionnaire -HSQ", (d) "Parental Stress Inventory-PSI", "Swedish Parenthood Stress Questionnaire-SPSQ", "Arizona Social Support Inventory" (e) "Parent Opinion Questionnaire-POQ". Interventions to ensure a more adequate parenting capacity should be focused on family planning: mothers with severe mental illness have poor knowledge about reproductive and contraception issues. Their pregnancies are mostly not planned. It is important for the family planning to be tailored according to the specific needs of schizophrenic mothers and to take into account the following issues: (a) the severity and the duration/chronicity of the disease, (b) the onset of the disease in relation to the gestational period, (c) the education of mothers with schizophrenia considering their double patient/mother role. An educational program should train the mother to recognize early signs of the disease, comply with medication, increase her empathy towards the baby and reduce any distorted perceptions about it. The treating, assessing, educating and preventing programs and interventions of mental health services should be continuous and supportive.
Tsalafoutas I.A.,Agios Savvas Hospital |
Georgolopoulou P.,Agios Savvas Hospital |
Abatzoglou I.,University General Hospital of Alexandroupolis
Physica Medica | Year: 2012
Purpose: To experimentally investigate the effect of the scan field of view (SFOV) selection and table height settings on the Computed Tomography Dose Index (CTDI) and the implications concerning patient effective and skin dose. Methods: Air-kerma length product (AKLP) measurements were carried out in a helical CT scanner using a pencil type dosimeter positioned in air and inside the holes of a head and a body phantom, using all available SFOV selections and different table height settings. Furthermore, using radiotherapy verification films placed on the CT table surface, the entrance surface air kerma (ESAK) profiles were derived with different SFOV and table height selections, both with and without a phantom on top of the films. Results: The AKLP is strongly dependent on the SFOV selection and the table height settings. Different SFOV selections correspond to the selection of different bowtie filters that shape the X-ray beam intensity, resulting in different ESAK values at the isocenter and at the other points within the scanning plane. With the off-center positioning the calculated CTDI values within the center and the periphery of the phantom change also, as a result of the different intensity and width of the X-ray beam to which are exposed to. Conclusions: The existing protocols for calculating effective dose are limited to only two patient anatomy-SFOV combinations and cannot account for off-center positioning. Therefore, more work will be required to estimate the effective and skin dose for non-standard SFOV-patient anatomy combinations and off-center patient positioning. © 2011 Associazione Italiana di Fisica Medica.
Drosos G.I.,Democritus University of Thrace |
Babourda E.,University General Hospital of Alexandroupolis |
Magnissalis E.A.,National and Kapodistrian University of Athens |
Giatromanolaki A.,Democritus University of Thrace |
And 2 more authors.
Injury | Year: 2012
The aim of this laboratory work was to study the compressive and flexural characteristics of various commercially available bone graft substitute (BGS) ceramic cements, in their initial as-mixed condition, and compare them to polymethylmethacrylate (PMMA). The tested biomaterials were two different calcium phosphate cements, two different calcium sulphate cements, one nanocrystalline hydroxyapatite and one PMMA cement. All biomaterials were prepared according to manufacturers instructions and the methodology described in ISO 5833 (2002) for acrylic bone cement was followed, as the one closest approaching in vivo requirements. All BGS cements had a brittle behaviour and when subjected to mechanical stress they all failed under sudden crack propagations in their bulk. Both in compression and bending, all BGS cements failed under loads lower than those of PMMA. In compression, the calcium sulphate extra strength cement showed a strength value of approximately 60% of PMMA, the other cements following at a distance. In bending, all BGS cements showed strengths below 22% of PMMA. However, due to limited number and fragility of specimens, calculated bending strengths can only be considered as indicative figures with limited comparative value. The results of this in vitro study showed a varying mechanical performance between tested BGS ceramic cements, whilst all of them exhibited lower compression and bending strength than the selected PMMA. These findings, of course, cannot be directly extrapolated to surgical or clinical implications, since the adopted in vitro context does not necessarily reflect the actual in vivo conditions met by such biomaterials. © 2011 Elsevier Ltd. All rights reserved.