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  • 1
    Keywords: Germany ; signal transduction ; HUMANS ; gene amplification ; ADULT ; DISEASE PROGRESSION ; female ; Male ; Aged ; Middle Aged ; Time Factors ; Proportional Hazards Models ; treatment outcome ; Gene Dosage ; Disease-Free Survival ; Adenocarcinoma/*drug therapy/enzymology/genetics/mortality/pathology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Deoxycytidine/administration & dosage/analogs & derivatives ; Drug Administration Schedule ; Esophageal Neoplasms/*drug therapy/enzymology/mortality/pathology ; Fluorouracil/administration & dosage/analogs & derivatives ; Kaplan-Meier Estimate ; Protein Kinase Inhibitors/administration & dosage/adverse effects/*therapeutic ; use ; Quinazolines/administration & dosage/adverse effects/*therapeutic use ; Receptor, ErbB-2/*antagonists & inhibitors/genetics/metabolism ; Stomach Neoplasms/*drug therapy/enzymology/genetics/mortality/pathology
    Abstract: INTRODUCTION: Human epidermal growth factor receptor 2 (HER2) amplification is present in a subgroup of gastroo-esophageal cancers (GCs). HER2 inhibition with trastuzumab has shown to improve outcomes in advanced disease. Lapatinib ditosylate (LAP), a dual anti-epidermal growth factor receptor (EGFR) and anti-HER2 tyrosine kinase inhibitor with preclinical activity against GC, has been approved in HER2-positive breast cancer. We aimed to study the activity of LAP in HER2-amplified GC. MATERIALS AND METHODS: Patients (pts) with HER2-positive (gene amplification or increased copy numbers based on predefined criteria) advanced GC were randomly allocated 1:1 to receive LAP 1250mg per day 1-21 plus capecitabine (CAP) 2000mg/m(2) on days 1-14 of a 21-day cycle or LAP 1500mg monotherapy day 1-21 after having failed on a platinum-based first-line therapy. HER2 status was assessed centrally. The primary end-point was the objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). We aimed to include 38 pts per arm to show an interesting response rate of 20% in either of the two arms. RESULTS: 37 pts were enrolled (18 to LAP+CAP, 19 to LAP). Pts had received a median of three prior treatment lines. 12 pts in the LAP+CAP group (67%) and 12 pts in the LAP group (63%) had received prior trastuzumab. Only two pts (11.1%; 95% confidence interval (CI): 1.37-34.7), both in the LAP+CAP arm, achieved an objective response. The study was closed prematurely for futility. Median time to progression was 42 (95% CI: 38-61) days in the LAP group and 83 (95% CI: 42-86) days in the LAP+CAP group. Other secondary efficacy end-points (progression-free and overall survival) were comparable in the two treatment groups. Rates of diarrhoea were higher with LAP+CAP (61%; 95% CI: 35-83) compared to 26% (95% CI 9-51) with LAP mono, whereas other adverse events were mostly similar between the groups (18 [100%] versus 17 [90%]). DISCUSSION: Lapatinib showed insufficient activity in HER2-amplified pretreated advanced GC. The safety profile of LAP or LAP+CAP was as expected with some more toxicity in the combination arm. (ClinicalTrials.gov Identifier, NCT01145404).
    Type of Publication: Journal article published
    PubMed ID: 25694417
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Chaos, Solitons and Fractals 4 (1994), S. 519-534 
    ISSN: 0960-0779
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Mathematics , Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 89 (1982), S. 11-12 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Psychosomatische Grundversorgung ; Fortbildung ; Hausärzte ; Beratung ; Psychiatrie ; Psychosomatik ; Key words Education ; Training program ; General practioners ; Psychosomatic medicine ; Psychiatry ; Primary care ; Continuous medical education
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Deficits in current approaches of psychosomatic and psychiatric education for general practitioners are reviewed. A skill-based training was developed in line with the four step counceling approach of the „PLISSIT” approach: The GP helps in first step („permission”) the patient to accept his problem and assesses informations about causing and maintaining factors of his symptomatology. In the second step he should provide information about the disorder and reverse misunderstanding and passivity (Limited Information). The GP’s should develop preliminary strategies for change in the third step („coping strategies”, „symptom management”; „special suggestions”) and preparate the intensive phase of therapy as the last step. First results of the evaluation of the training program are presented demonstrate the effectiveness and acceptance of the education programm.
    Notes: Zusammenfassung Ausgehend von einer Analyse der Schwächen aktueller Ansätze der psychosomatischen Grundversorgung wird einerseits ein Ansatz vorgestellt, der störungsspezifisch im Rahmen eines Mehrebenenmodells pharmakologische und verbale Intervention aufeinander bezieht. Andererseits werden im Sinne eines zeitökonomisch abgestuften Vorgehens verschiedene Phasen durch das zugrundegelegte PLISSIT-Modell differenziert: In der Permission-Phase geht es um die Akzeptanzvermittlung und Problemanalyse hinsichtlich der vom Patienten geschilderten Beschwerden, in der Phase der „limited information” um die dialogische Erarbeitung eines Störungsmodells und den Aufbau einer aktiven Änderungsmotivation, in der Phase der „special suggestions” erfolgt eine konkrete Anleitung zur Selbstbeobachtung und -protokollierung des Problemverhaltens sowie die Vermittlung von Strategien zum Symptommanagement; in der letzten Phase der „intensive therapy” geht es um die Indikationsstellung und den Motivationsaufbau zur fachärztlichen bzw. fachpsychotherapeutischen Weiterbehandlung. Empirische Ergebnisse zur Evaluation des Weiterbildungskonzeptes an über 200 Teilnehmern werden referiert.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 10 (1996), S. 156-162 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Homöpathie ; Kopfschmerzen ; Überblick ; Migräne ; Key words Homeopathy ; Headache ; Migraine ; Review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Homeopathy as an alternative to conventional therapy is becoming increasingly popular. Although interest is rising, little is known about the real effectiveness of homeopathic therapy in headaches. Three studies addressing this question are discussed: an Italian migraine study, the London migraine study and our own, the Munich headache trial. While the first one reported very high effects, the best ones known in the literature, the results of the other two trials do not endorse this first finding. The London trial did not show any effect other than placebo, although a different time trend was reported. The Munich study failed to show any difference between homeopathy and placebo whatsoever. The merits and shortcomings of these studies are discussed. At present, we do not have any evidence that homeopathic therapy has any effect other than a placebo effect. However, this can be very impressive sometimes. We do not know which variables are correlated with placebo effectiveness, and we do not have any data on real-type homeopathy outside a trial setting, as there are no data available.
    Notes: Zusammenfassung Homöopathie wird in der Bevölkerung auch und gerade zur Behandlung von Kopfschmerzen immer populärer. Im Gegensatz hierzu steht die mangelnde wissenschaftliche Durchdringung. Wir diskutieren 3 Studien, die zur Effektivität von homöopathischer Therapie bei Migräne und Kopfschmerzen durchgeführt wurden: die italienische und die Londoner Migränestudie und die Münchener Kopfschmerzstudie. Während die erste von geradezu sensationellen Heilungsraten berichtet, konnten die beiden anderen Studien diese Ergebnisse nicht replizieren. Weder die Londoner noch die Münchener Studie fanden Hinweise für einen Unterschied zwischen Homöopathie und Plazebotherapie. Allerdings können beachtenswerte klinische Erfolge auftreten, über deren Zustandekommen wir derzeit wenig wissen. Auch fehlen uns Daten darüber, wie effektiv homöopathische Therapie in der normalen, unkontrollierten Praxis ist.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0630
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The problem of output-coupling optimization of a transversely or longitudinally pumped dye laser is treated in terms of a rate equation approach under steady state considerations. The theoretical study considers the spatial variation of the gain distribution and such typical features of a dye laser as reabsorption, triplet effects and excited state absorption. Numerical results obtained with realistic values of typical laser parameters (cross-sections for stimulated emission and reabsorption, number density of active molecules etc.) indicate that a higher degree of output coupling and consequently higher output powers are feasible upon a complete consideration of the spatial gain distribution
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1434-6036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A systematic algorithm for finding solutions of Fokker Planck systems with time-dependent drift and fluctuation coefficients is developed. The solutions lag behind the adiabatic quasistationary distribution. This delay effect vanishes for slowly varying control parameters. In a first example the evolution of the phase transition from a monostable to a bistable system is treated. There is a fluctuation enhancement and the delay of the probability distribution leads to a transient central peak. In a second example a linear model with time-dependently shifted drift is considered. The introduced approximation scheme reproduces the exact solution already in first order.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1434-6036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The influence of amplified spontaneous emission (ASE) on the operation of laser amplifiers is studied with a photon-transport equation approach. Nonsaturable losses are included in our considerations. Two different amplifier geometries are considered, the single-pass- and the double-pass configuration. In both cases closed equations for the stage gain and the ASE-output are derived. The feedback of ASE leads to a new saturation behavior of the gain in dependence of the pump intensity.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1434-6036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Two methods for finding stationary solutions of discrete master equation in general cases without detailed balance are set up and compared for the case of the Laser equation. The first method starts from a reduced master equation obtained for appropriate forms of the Liouvillean, the second from a variational principle for the stationary solution of the full master equation. In the Laser case, both methods lead to forms of the stationary solution essentially equivalent to the result of Dohm.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1434-6036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We introduce “transition factors” and derive equations for them which are equivalent to the originalN-dimensional discrete master equation. After transition to continuous variables we obtain nonlocal partial differential equations for these transition factors which are slowly varying variables. Finally we consider a chemical reaction system. Using this method the corresponding master equation is exactly solvable in a very simple manner.
    Type of Medium: Electronic Resource
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