Abstract
Background: Trastuzumab (Herceptin®; H) is a standard component of adjuvant treatment in patients with HER2+ early breast cancer (eBC) and is supported by all major treatment guidelines. The ...efficacy and safety of Herceptin intravenous (H IV) and Herceptin subcutaneous (H SC) have been shown to be comparable. The main advantage of SC administration is its shorter administration time. Administration at home for selected patients will allow greater independence and may lead to an improved quality of life. In this study, we assessed the safety and tolerability of H SC administered at home by a healthcare professional (HCP) in patients with HER2+ eBC.
Methods: Patients with HER2+ eBC who previously completed 6 cycles of H IV could be included in the study to receive 12 additional cycles of H for a total of 18 cycles. The 12 additional 3-week cycles consisted of 3 cycles of H IV in the hospital (6 mg/kg; cycles 7 to 9; period 1); 3 cycles of H SC in the hospital (600 mg; cycles 10 to 12; period 2); and 6 cycles of H SC administered in the home by a HCP (600 mg; cycles 13 to 18; period 3). Patients are being followed for a total of 24 months after their last treatment. Safety is being assessed from the adverse events (AEs) reported during the study. Patient-reported outcomes were obtained from validated questionnaires for: the satisfaction and quality of the treatments and care, and for symptom severity (0 absent to 10 worst). HCPs also reported on their experiences with both treatments.
Results: A total of 102 patients were treated in the study between November 2013 and July 2015 and will be followed for safety and efficacy through July 2017. The primary analysis reported here was done after the last 4-week post-treatment follow-up was completed (September 2015). Patient mean age at baseline was 54.4±12.3 (SD) years. A total of 91 (89%) patients reported 549 AEs: 535 (97%) of these were grade 1 or 2 and 194 (35%) were considered treatment related. The proportions of patients with at least one related AE were 7% for H IV period 1, 32% for H SC period 2, and 47% for H SC period 3, which was twice as long as periods 1 or 2. A total of 8 serious AEs were reported in 8 patients (2 each in periods 1 and 2; 4 in period 3). Prior to the first at-home SC administration (cycle 13), 99% of patients were satisfied to a large or very large extent with the IV and SC treatments at the hospital. At cycle 17, 100% of patients were satisfied to a large or very large extent with the SC treatment at home, and 100% of patients thought treatment at home was beneficial to a large or very large extent. In all 3 treatment periods, maximum mean scores were 3.0−3.8 for the most severe symptoms (fatigue, disturbed sleep, and numbness or tingling). All HCPs considered both administration routes to be fairly easy or very easy, and SC administration to be quicker and require fewer preparation resources.
Conclusions: The safety analyses and patient-reported outcomes recorded in this study indicate that H SC administered by a HCP at home instead of at the hospital was not associated with any new safety signals and was considered beneficial by the patients and HCPs.
Citation Format: Cocquyt VF, Martinez-Mena CL, Martens MT, D'Hondt RG, Graas M-PL, Evron E, Fried G, Ben-Baruch NE, Dijkstra AC, Van De Walle EI. BELIS: Safety and tolerability of at home administration of trastuzumab (Herceptin®) subcutaneous for the treatment of patients with HER2-positive early breast cancer abstract. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-17.
Neuromodulation has been used to treat voiding dysfunction in adults. Due to its invasiveness it has rarely been used in children until now with the availability of transcutaneous neurostimulation. ...We evaluated clinical effects of transcutaneous neuromodulation on detrusor overactivity in children with the urge syndrome.
Between May 1, 1998 and February 28, 1999, 15 girls (mean age 10.2 years) and 26 boys (mean age 10.7 years) with proved detrusor hyperactivity on videourodynamic study underwent neuromodulation. All children had been given anticholinergic therapy previously. Neurostimulation only was used in children in whom anticholinergics had no effect and those who had significant side effects. Anticholinergics were continued in children in whom they had a partial effect. Stimulation of 2 Hz. was applied for 2 hours every day. Surface electrodes were placed at the level of sacral root S3. After 1 month of trial stimulation those children who responded continued the treatment for 6 months, and were evaluated every 2 months.
Of the 41 children 15 boys and 13 girls responded after 1 month of trial therapy with an increase in bladder capacity, decrease in urgency, decrease in incontinence and/or better sensitivity. Of the 13 children who did not respond 9 lacked motivation and 4 had no clinical effect despite motivation. After 6 months of therapy a significant increase in bladder capacity, decrease in voiding frequency and decrease in incontinence periods were noted. Adverse effects were not observed. One year after therapy relapse was noted in 7 patients, leaving 21 of 41 children definitively cured.
Although preliminary, our results indicate that transcutaneous neuromodulation can improve symptoms of detrusor overactivity, as response to stimulation was noted in 76% of our patients and 56% were cured after 1 year. This therapeutic option is attractive for children because of its noninvasiveness and absence of adverse effects.
A 3D model for the prediction of the effective thermal conductivity of porous building blocks is introduced. Simulations are performed directly on the microstructure using voxel images and the ...finite element technique. Very good agreement with analytical solutions is achieved. The model is used to investigate the miscalculation effect of 2D simulations, clearly indicating the need for a 3D model. Furthermore, a method for incorporating radiative heat transfer at the microscale is implemented and applied on a synthetic sample, demonstrating the influence of thermal radiation on the effective thermal conductivity. Ein Vorhersagemodell fur die Wärmeleitfähigkeit poröser Bausteine. Ein 3D-Modell zur Vorhersage der effektiven Wärmeleitfähigkeit poröser Bausteine wird vorgestellt. Simulationen werden direkt in der Mikrostruktur mittels Voxel-Bildern und Finite-Elemente-Methode durchgefuhrt. Sehr gute Übereinstimmungen mit analytischen Verfahren werden erreicht. Das Modell wird verwendet, um die Fehlberechnungswirkung von 2D-Simulationen zu untersuchen, welche klar das Erfordernis eines 3D-Modells zeigen. Zudem wird eine Methode zur Einbeziehung strahlungsgebundener Wärmeubertragung im Mikrobereich umgesetzt und auf einen synthetischen Prufkörper angewandt. Dies zeigt den Einfluss von Wärmestrahlung auf die effektive Wärmeleitfähigkeit.
"Als George W. Bush im Januar 2009 das Präsidentenamt verließ, schien allgemeine Übereinstimmung darüber zu herrschen, dass seine Afrikapolitik einer seiner wenigen Erfolge gewesen ist, da selbst ...harte Kritiker der Regierung dies widerwillig einräumen mussten. Tatsächlich stieg während seiner Amtszeit das Engagement der USA auf dem afrikanischen Kontinent sehr deutlich an. Allein die Entwicklungshilfe wurde verdreifacht. Das Erbe der Regierung Bush ist weit weniger positiv, als gemeinhin angenommen wird. Denn trotz der deutlichen Erhöhung der US-Entwicklungshilfe für Afrika, blieb die US-Afrikapolitik mit grundlegenden Mängeln behaftet, die sich unter Bush noch verschärft hatten und nun für die neue Politik von Obama/ Clinton eine erhebliche Belastung darstellen. Die Regierung Bush hat es versäumt, die US-Politik gegenüber Afrika strategisch klar und umfassend zu definieren; dieser fehlt nach wie vor strategische Kohärenz. Dabei hat sich die ohnehin schon vorhandene institutionelle und programmatische Zersplitterung der US-Afrikapolitik erhöht und die United States Agency for International Development (USAID) wurde weiter geschwächt. Die diplomatische Präsenz der USA in Afrika und die administrativen Kapazitäten des Afrikareferats in Washington sind besonders deutlich zurückgegangen. Demgegenüber hat der sicherheitspolitische Einfluss des Verteidigungsministeriums erheblich zugenommen. Aufgrund dieser institutionellen Schwäche der US-Afrikapolitik, der geringen strategischen Bedeutung Afrikas und der haushaltspolitischen Restriktionen angesichts der Wirtschafts- und Finanzkrise sind unter Obama kaum entscheidende Änderungen zu erwarten. Allenfalls kann der Schwerpunkt verschoben werden, weg von der sicherheitspolitischen Agenda und hin zu Multilateralismus, verknüpft mit einem diplomatischen Stilwandel - wobei ein Imagegewinn der USA in Afrika schon ein Erfolg wäre." (Autorenreferat)
PDF
