A Thiel1, J Schetelig2, W Pönisch3, K Schäfer-Eckart4, W Aulitzky5, N Peter6, A Schulze7, G Maschmeyer8, S Neugebauer9, R Herbst1, A Hänel1, A Morgner1, F Kroschinsky10, M Bornhäuser10, T Lange3, M Wilhelm4, D Niederwieser3, G Ehninger10, F Fiedler1, M Hänel11. 1. Internal Medicine III, Department of Hematology, Oncology, Stem Cell Transplantation, Klinikum Chemnitz gGmbH, Chemnitz. 2. Department of Internal Medicine I, University Hospital Carl Gustav Carus, University of Dresden, Dresden DKMS, German Bone Marrow Donor Center, Clinical Trials Unit, Dresden. 3. Department of Hematology, Clinical Oncology and Hemostasiology, University of Leipzig, Leipzig. 4. Medical Clinic 5, Hematology and Oncology, Klinikum Nuernberg, Nuernberg. 5. Hematology and Oncology, Robert Bosch Krankenhaus, Stuttgart. 6. Department of Oncology, Klinikum Carl Thiem, Cottbus. 7. Medical Clinic, Hematology/Oncology, Helios Clinic Erfurt GmbH, Erfurt. 8. Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam. 9. WiSP Research, Langenfeld, Germany. 10. Department of Internal Medicine I, University Hospital Carl Gustav Carus, University of Dresden, Dresden. 11. Internal Medicine III, Department of Hematology, Oncology, Stem Cell Transplantation, Klinikum Chemnitz gGmbH, Chemnitz m.haenel@skc.de.
Abstract
BACKGROUND: For patients with primary refractory or relapsed acute myeloid leukemia (AML), no treatment of choice has until now been defined to date. Cytarabine (Ara-C) is a key drug in the treatment of AML patients, there is still uncertainly regarding its optimal dose and infusion schedule. The aim of this study is to examine the impact of the Ara-C infusion schedule used as part of an intensive salvage regimen, in patients with relapsed or refractory AML. PATIENTS AND METHODS: A total of 252 adult patients (median age 59 years) with relapsed or refractory AML were randomly allocated to receive either Mito-FLAG with Ara-C as bolus (B) (1000 mg/m(2) over 1 h, every 12 h, days 1-5), or continuous infusion (CI) (150 mg/m(2) over 24 h, days 1-5) in combination with mitoxantrone, fludarabine, and granulocyte colony-stimulating factor (G-CSF). Autologous or allogeneic hematopoietic stem-cell transplantation was offered as consolidation therapy. Primary end point was the rate of complete remissions (CRs) after the first cycle of Mito-FLAG. RESULTS: The CR rates after Mito-FLAG (B) and Mito-FLAG (CI) were 54% and 43%, respectively (P = 0.1). There was no statistical difference between rates of grade 3/4 neutropenia, thrombocytopenia, mucositis, renal, and liver toxicity. More infections occurred, however, after Mito-FLAG (B) compared with Mito-FLAG (CI) (80% versus 69%, P = 0.01). The early death rate by day 42 was 13% in both arms. Median disease-free survival was comparable in the two arms (7.8 versus 7.1 months, P = 0.53) as was overall survival (7.1 versus 6.6 months, P = 0.53). CONCLUSION: A 5-day course of Ara-C 2 × 1000 mg/m(2) administered as bolus versus Ara-C 150 mg/m(2) administered by CI (in combination with mitoxantrone, fludarabine, and G-CSF), resulted in a nonsignificant trend in response rates in favor of Mito-FLAG (B) at the selected dose levels, but no differences in the survival outcome in relapsed or refractory AML. CLINICAL TRIAL NUMBER: LN_NN_2004_39/EudraCT number 2014-000083-18.
RCT Entities:
BACKGROUND: For patients with primary refractory or relapsed acute myeloid leukemia (AML), no treatment of choice has until now been defined to date. Cytarabine (Ara-C) is a key drug in the treatment of AMLpatients, there is still uncertainly regarding its optimal dose and infusion schedule. The aim of this study is to examine the impact of the Ara-C infusion schedule used as part of an intensive salvage regimen, in patients with relapsed or refractory AML. PATIENTS AND METHODS: A total of 252 adult patients (median age 59 years) with relapsed or refractory AML were randomly allocated to receive either Mito-FLAG with Ara-C as bolus (B) (1000 mg/m(2) over 1 h, every 12 h, days 1-5), or continuous infusion (CI) (150 mg/m(2) over 24 h, days 1-5) in combination with mitoxantrone, fludarabine, and granulocyte colony-stimulating factor (G-CSF). Autologous or allogeneic hematopoietic stem-cell transplantation was offered as consolidation therapy. Primary end point was the rate of complete remissions (CRs) after the first cycle of Mito-FLAG. RESULTS: The CR rates after Mito-FLAG (B) and Mito-FLAG (CI) were 54% and 43%, respectively (P = 0.1). There was no statistical difference between rates of grade 3/4 neutropenia, thrombocytopenia, mucositis, renal, and liver toxicity. More infections occurred, however, after Mito-FLAG (B) compared with Mito-FLAG (CI) (80% versus 69%, P = 0.01). The early death rate by day 42 was 13% in both arms. Median disease-free survival was comparable in the two arms (7.8 versus 7.1 months, P = 0.53) as was overall survival (7.1 versus 6.6 months, P = 0.53). CONCLUSION: A 5-day course of Ara-C 2 × 1000 mg/m(2) administered as bolus versus Ara-C 150 mg/m(2) administered by CI (in combination with mitoxantrone, fludarabine, and G-CSF), resulted in a nonsignificant trend in response rates in favor of Mito-FLAG (B) at the selected dose levels, but no differences in the survival outcome in relapsed or refractory AML. CLINICAL TRIAL NUMBER: LN_NN_2004_39/EudraCT number 2014-000083-18.
Authors: Regina Mühleck; Sebastian Scholl; Inken Hilgendorf; Karin Schrenk; Jakob Hammersen; Jochen J Frietsch; Maximilian Fleischmann; Herbert G Sayer; Anita Glaser; Andreas Hochhaus; Ulf Schnetzke Journal: J Cancer Res Clin Oncol Date: 2021-10-05 Impact factor: 4.322
Authors: Luo Rongmu; Zhang Xiaomei; Du Zhenlan; Wang Ya; Chen Wei; Si Yingjian; Gu Wenjing; Xing Guosheng; Wang Yang; Da Wanming Journal: Oncotarget Date: 2017-12-04
Authors: Haifa Kathrin Al-Ali; Dietger Niederwieser; Thomas Heinicke; Rainer Krahl; Christoph Kahl; Michael Cross; Sebastian Scholl; Hans-Heinrich Wolf; Detlev Hähling; Ute Hegenbart; Norma Peter; Antje Schulze; Axel Florschütz; Volker Schmidt; Kolja Reifenrath; Niklas Zojer; Christian Junghanss; Herbert G Sayer; Georg Maschmeyer; Christian Späth; Andreas Hochhaus; Thomas Fischer Journal: Ann Hematol Date: 2021-07-07 Impact factor: 3.673