C Röllig1, M Kramer2, M Gabrecht3, M Hänel4, R Herbst4, U Kaiser5, N Schmitz6, J Kullmer7, S Fetscher8, H Link9, L Mantovani-Löffler10, U Krümpelmann11, T Neuhaus12, F Heits13, H Einsele14, B Ritter15, M Bornhäuser2, J Schetelig16, C Thiede2, B Mohr2, M Schaich17, U Platzbecker2, K Schäfer-Eckart18, A Krämer19, W E Berdel20, H Serve21, G Ehninger2, U S Schuler2. 1. Medical Department I, University Hospital of the Technical University Dresden, Dresden, Germany. Electronic address: christoph.roellig@uniklinikum-dresden.de. 2. Medical Department I, University Hospital of the Technical University Dresden, Dresden, Germany. 3. Medical Department I, University Hospital of the Technical University Dresden, Dresden, Germany; University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany. 4. Department for Internal Medicine III, Klinikum Chemnitz, Chemnitz, Germany. 5. Medical Department II, St. Bernward Hospital, Hildesheim, Germany. 6. Department of Haematolog, Oncology and Stem Cell Transplantation, Asklepios Klinik St. Georg, Hamburg, Germany. 7. Medical Department II, DIAKO, Bremen, Germany. 8. Medical Department III, Sana Kliniken, Lübeck, Germany. 9. Department for Internal Medicine 1, Westpfalzklinikum, Kaiserslautern, Germany. 10. Department for Medical Oncology and Haematology, Klinikum St. Georg, Leipzig, Germany. 11. Department for Haematolog, Oncology and Palliative Care, Klinikum Bielefeld, Bielefeld, Germany. 12. Department for Haemaolog, Medical Oncology and Palliative Care, St. Vincenz Hospital, Limburg, Germany. 13. Department for Haematology and Oncolog, Stem Cell Transplantation, Agaplesion Diakonieklinikum, Rotenburg, Germany. 14. Medical Department II, University Hospital Würzburg, Würzburg, Germany. 15. Department for Oncology and Haematology, Klinikum Kassel, Kassel, Germany. 16. Medical Department I, University Hospital of the Technical University Dresden, Dresden, Germany; DKMS, German Bone Marrow Donor Center, Dresden, Germany. 17. Department for Haematolog, Oncology and Palliative Care, Rems-Murr-Klinikum, Winnenden, Germany. 18. Department for Internal Medicine 5, Paracelsus Medical University, Nürnberg, Germany. 19. Department of Internal Medicine V, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany. 20. Medical Department A, University Hospital Münster, Münster, Germany. 21. Medical Department II, University Hospital Frankfurt, Frankfurt/Main, Germany; German Cancer Consortium and DKFZ, Heidelberg, Germany.
Abstract
Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA). Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513). Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.
RCT Entities:
Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA). Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513). Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AMLpatients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AMLpatients.
Authors: Sebastian Stasik; Jan-Niklas Eckardt; Michael Kramer; Christoph Röllig; Alwin Krämer; Sebastian Scholl; Andreas Hochhaus; Martina Crysandt; Tim H Brümmendorf; Ralph Naumann; Björn Steffen; Volker Kunzmann; Hermann Einsele; Markus Schaich; Andreas Burchert; Andreas Neubauer; Kerstin Schäfer-Eckart; Christoph Schliemann; Stefan Krause; Regina Herbst; Mathias Hänel; Norbert Frickhofen; Richard Noppeney; Ulrich Kaiser; Claudia D Baldus; Martin Kaufmann; Zdenek Rácil; Uwe Platzbecker; Wolfgang E Berdel; Jiri Mayer; Hubert Serve; Carsten Müller-Tidow; Gerhard Ehninger; Martin Bornhäuser; Johannes Schetelig; Jan M Middeke; Christian Thiede Journal: Blood Adv Date: 2021-09-14
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Authors: Jan-Niklas Eckardt; Sebastian Stasik; Michael Kramer; Christoph Röllig; Alwin Krämer; Sebastian Scholl; Andreas Hochhaus; Martina Crysandt; Tim H Brümmendorf; Ralph Naumann; Björn Steffen; Volker Kunzmann; Hermann Einsele; Markus Schaich; Andreas Burchert; Andreas Neubauer; Kerstin Schäfer-Eckart; Christoph Schliemann; Stefan W Krause; Regina Herbst; Mathias Hänel; Norbert Frickhofen; Richard Noppeney; Ulrich Kaiser; Claudia D Baldus; Martin Kaufmann; Zdenek Rácil; Uwe Platzbecker; Wolfgang E Berdel; Jiří Mayer; Hubert Serve; Carsten Müller-Tidow; Gerhard Ehninger; Friedrich Stölzel; Frank Kroschinsky; Johannes Schetelig; Martin Bornhäuser; Christian Thiede; Jan Moritz Middeke Journal: Cancers (Basel) Date: 2021-04-26 Impact factor: 6.639
Authors: Jan-Niklas Eckardt; Jan Moritz Middeke; Karsten Wendt; Martin Bornhäuser; Sebastian Riechert; Tim Schmittmann; Anas Shekh Sulaiman; Michael Kramer; Katja Sockel; Frank Kroschinsky; Ulrich Schuler; Johannes Schetelig; Christoph Röllig; Christian Thiede Journal: Leukemia Date: 2021-09-08 Impact factor: 11.528
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Authors: Jan M Middeke; Klaus H Metzeler; Christoph Röllig; Michael Krämer; Jan-Niklas Eckardt; Sebastian Stasik; Philipp A Greif; Karsten Spiekermann; Maja Rothenberg-Thurley; Utz Krug; Jan Braess; Alwin Krämer; Andreas Hochhaus; Tim H Brümmendorf; Ralph Naumann; Björn Steffen; Hermann Einsele; Markus Schaich; Andreas Burchert; Andreas Neubauer; Dennis Görlich; Cristina Sauerland; Kerstin Schäfer-Eckart; Christoph Schliemann; Stefan W Krause; Mathias Hänel; Norbert Frickhofen; Richard Noppeney; Ulrich Kaiser; Martin Kaufmann; Desiree Kunadt; Bernhard Wörmann; Katja Sockel; Malte von Bonin; Tobias Herold; Carsten Müller-Tidow; Uwe Platzbecker; Wolfgang E Berdel; Hubert Serve; Claudia D Baldus; Gerhard Ehninger; Johannes Schetelig; Wolfgang Hiddemann; Martin Bornhäuser; Friedrich Stölzel; Christian Thiede Journal: Blood Adv Date: 2022-03-08
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Authors: Sabine Kayser; Michael Kramer; David Martínez-Cuadrón; Justin Grenet; Klaus H Metzeler; Zuzana Sustkova; Marlise R Luskin; Andrew M Brunner; Michelle A Elliott; Cristina Gil; Sandra Casal Marini; Zdeněk Ráčil; Petr Cetkovsky; Jan Novak; Alexander E Perl; Uwe Platzbecker; Friedrich Stölzel; Anthony D Ho; Christian Thiede; Richard M Stone; Christoph Röllig; Pau Montesinos; Richard F Schlenk; Mark J Levis Journal: Haematologica Date: 2022-04-01 Impact factor: 9.941