von Bernhard Wörmann ; Carsten Bokemeyer ; Thomas Burmeister ; Claus-Henning Köhne ; Matthias Schwab ; Dirk Arnold ; Jens-Uwe Blohmer ; Markus Borner ; Sara Brucker ; Ingolf Cascorbi ; Thomas Decker ; Maike de Wit ; Andreas Dietz ; Hermann Einsele ; Wolfgang Eisterer ; Gunnar Folprecht ; Wolfgang Hilbe ; Jürgen Hoffmann ; Wolfgang Knauf ; Volker Kunzmann ; Carlo R. Largiadèr ; Sylvie Lorenzen ; Diana Lüftner ; Markus Moehler ; Markus M. Nöthen ; Christian Pox ; Anke Reinacher-Schick ; Anton Scharl ; Brigitte Schlegelberger ; Thomas Seufferlein ; Marianne Sinn ; Matthias Stroth ; Ingo Tamm ; Lorenz Trümper ; Martin Wilhelm ; Ewald Wöll ; Ralf-Dieter Hofheinz
<b><i>Background:</i></b> 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%. <b><i>Summary:</i></b> Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (<i>DPYD</i>). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. <b><i>Key Messages:</i></b> (i) Patients should be tested for the 4 most common genetic <i>DPYD</i> variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.
Oncology research and treatment Basel : Karger, 2014 43(2020), 11, Seite 628-636 Online-Ressource
Published Online October 9, 2019 ; Gesehen am 15.04.2020
Background - Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. - Methods - We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18-70 years, had acute myeloid leukaemia in first or consecutive complete haematological remission (blast counts <5% in bone marrow) or myelodysplastic syndrome (blast counts <20% in bone marrow), Karnofsky index of 60% or higher, and were indicated for allogeneic HSCT but considered at an increased risk for standard myeloablative preparative regimens based on age (≥50 years), an HSCT-specific comorbidity index of more than 2, or both. Patients were randomly assigned (1:1) to receive either intravenous 10 g/m2 treosulfan daily applied as a 2-h infusion for 3 days (days -4 to -2) or 0·8 mg/kg busulfan applied as a 2-h infusion at 6-h intervals on days -4 and -3. Both groups received 30 mg/m2 intravenous fludarabine daily for 5 days (days -6 to -2). The primary outcome was event-free survival 2 years after HSCT. The non-inferiority margin was a hazard ratio (HR) of 1·3. Efficacy was assessed in all patients who received treatment and completed transplantation, and safety in all patients who received treatment. The study is registered with EudraCT (2008-002356-18) and ClinicalTrials.gov (NCT00822393). - Findings - Between June 13, 2013, and May 3, 2016, 476 patients were enrolled (240 in the busulfan group received treatment and transplantation, and in the treosulfan group 221 received treatment and 220 transplanation). At the second preplanned interim analysis (Nov 9, 2016), the primary endpoint was met and trial was stopped. Here we present the final confirmatory analysis (data cutoff May 31, 2017). Median follow-up was 15·4 months (IQR 8·8-23·6) for patients treated with treosulfan and 17·4 months (6·3-23·4) for those treated with busulfan. 2-year event-free survival was 64·0% (95% CI 56·0-70·9) in the treosulfan group and 50·4% (42·8-57·5) in the busulfan group (HR 0·65 [95% CI 0·47-0·90]; p<0·0001 for non-inferiority, p=0·0051 for superiority). The most frequently reported grade 3 or higher adverse events were abnormal blood chemistry results (33 [15%] of 221 patients in the treosulfan group vs 35 [15%] of 240 patients in the busulfan group) and gastrointestinal disorders (24 [11%] patients vs 39 [16%] patients). Serious adverse events were reported for 18 (8%) patients in the treosulfan group and 17 (7%) patients in the busulfan group. Causes of deaths were generally transplantation-related. - Interpretation - Treosulfan was non-inferior to busulfan when used in combination with fludarabine as a conditioning regimen for allogeneic HSCT for older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. The improved outcomes in patients treated with the treosulfan-fludarabine regimen suggest its potential to become a standard preparative regimen in this population. - Funding - medac GmbH.
The lancet. Haematology London [u.a.] : Elsevier, 2014 7(2020), 1, Seite e28-e39 Online-Ressource
Speyer, Wilhelm 1887-1952 -- Interviews; Benjamin, Walter 1892-1940 -- Interviews; Speyer, Wilhelm 1887-1952 -- Criticism and interpretation; Speyer, Wilhelm 1887-1952 -- Authorship -- Collaboration; Benjamin, Walter 1892-1940 -- Dramatic works; Benjamin, Walter 1892-1940 -- Authorship -- Collaboration; Dramatik; Theaterstück
Texte -- Es geht : Aber es ist auch danach! [1929] -- Rezepte für Komödienschreiber : Gespräch zwischen Wilhelm Speyer und Walter Benjamin [1930] -- Jeder einmal in Berlin! [1930] -- Ein Mantel, ein Hut, ein Handschuh [1933] -- Kommentar -- Zu "Es geht : Aber es ist auch danach!" -- Zu "Rezepte für Komödienschreiber : Gespräch zwischen Wilhelm Speyer und Walter Benjamin" -- Zu "Jeder einmal in Berlin!" -- Zu "Ein Mantel, ein Hut, ein Handschuh" -- Nachwort -- Literaturverzeichnis -- Dank..
von Ralph W. König ; Thomas Kretschmer ; Maria Teresa Pedro ; Christian Bischoff ; Wilhelm Schulte-Mattler ; Heinrich Kele ; Philipp Bäumer ; Martin Bendszus ; Mirko Pham
von Maximilian Hemgesberg ; Bilguun Bayarmagnai ; Nadine Jacobs ; Sarah Bay ; Sascha Follmann ; Christian Wilhelm ; Zhou Zhou ; Martin Hartmann ; Gunther Wittstock ; Werner R. Thiel
von Jörg Enderlein ; Thomas Dertinger ; Iris von der Hocht ; Anastasia Loman ; Ingo Gregor ; Karl-Wilhelm Koch ; Konstantin E. Komolov ; Felix Koberling ; Rainer Erdmann
