Cancers (Feb 2021)
Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS
- Jeroen Janssen,
- Bob Löwenberg,
- Markus Manz,
- Mario Bargetzi,
- Bart Biemond,
- Peter von dem Borne,
- Dimitri Breems,
- Rolf Brouwer,
- Yves Chalandon,
- Dries Deeren,
- Anna Efthymiou,
- Bjørn-Tore Gjertsen,
- Carlos Graux,
- Michael Gregor,
- Dominik Heim,
- Urs Hess,
- Mels Hoogendoorn,
- Aurelie Jaspers,
- Asiong Jie,
- Mojca Jongen-Lavrencic,
- Saskia Klein,
- Marjolein van der Klift,
- Jürgen Kuball,
- Danielle van Lammeren-Venema,
- Marie-Cecile Legdeur,
- Arjan van de Loosdrecht,
- Johan Maertens,
- Marinus van Marwijk Kooy,
- Ine Moors,
- Marten Nijziel,
- Florence van Obbergh,
- Margriet Oosterveld,
- Thomas Pabst,
- Marjolein van der Poel,
- Harm Sinnige,
- Olivier Spertini,
- Wim Terpstra,
- Lidwine Tick,
- Walter van der Velden,
- Marie-Christiane Vekemans,
- Edo Vellenga,
- Okke de Weerdt,
- Peter Westerweel,
- Georg Stüssi,
- Yvette van Norden,
- Gert Ossenkoppele
Affiliations
- Jeroen Janssen
- Amsterdam University Medical Centers, loc. VUmc, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Bob Löwenberg
- Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
- Markus Manz
- Universitätsspital Zürich, 8091 Zürich, Switzerland
- Mario Bargetzi
- Kantonsspital Aarau, 5001 Aarau Aarau, Switzerland
- Bart Biemond
- Amsterdam University Medical Centers, loc. AMC, 1105 AZ Amsterdam, The Netherlands
- Peter von dem Borne
- Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
- Dimitri Breems
- Ziekenhuis Netwerk Antwerpen, 2000 Antwerp, Belgium
- Rolf Brouwer
- Reinier de Graaf Hospital, 2625 AD Delft, The Netherlands
- Yves Chalandon
- Division of Hematology, Department of Oncology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, 1211 Geneve, Switzerland
- Dries Deeren
- AZ Delta, 8800 Roeselare, Belgium
- Anna Efthymiou
- Hôpital Fribourgeois, 1708 Fribourg, Switzerland
- Bjørn-Tore Gjertsen
- Haukeland University Hospital, 5021 Bergen, Norway
- Carlos Graux
- Mont Godinne, 5530 Yvoir, Belgium
- Michael Gregor
- Luzerner Kantonsspital, 6004 Luzern, Switzerland
- Dominik Heim
- University Hospital of Basel, 4031 Basel, Switzerland
- Urs Hess
- Kantonsspital St. Gallen, 9007 St.Gallen, Switzerland
- Mels Hoogendoorn
- Medisch Centrum Leeuwarden, 8934 AD Leeuwarden, The Netherlands
- Aurelie Jaspers
- Citadelle Hospital, 4000 Liege, Belgium
- Asiong Jie
- Zuyderland MC, Postbus 5500, 6130 MB Sittard, The Netherlands
- Mojca Jongen-Lavrencic
- Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
- Saskia Klein
- Meander Medical Center, 3813 TZ Amersfoort, The Netherlands
- Marjolein van der Klift
- Amphia Hospital, 4819 EV Breda, The Netherlands
- Jürgen Kuball
- University Medical Center, 3584 CX Utrecht, The Netherlands
- Danielle van Lammeren-Venema
- Haga Hospital, 2545 AA Den Haag, The Netherlands
- Marie-Cecile Legdeur
- Medisch Spectrum Twente, 7512 KZ Enschede, The Netherlands
- Arjan van de Loosdrecht
- Amsterdam University Medical Centers, loc. VUmc, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Johan Maertens
- University Hospital Gasthuisberg, 3000 Leuven, Belgium
- Marinus van Marwijk Kooy
- Isala Clinics, 8025 AB Zwolle, The Netherlands
- Ine Moors
- Gent University Hospital, 9000 Gent, Belgium
- Marten Nijziel
- Catharina Hospital, 5623 EJ Eindhoven, The Netherlands
- Florence van Obbergh
- Hospital Jolimont, 7100 Haine-Saint-Paul, Belgium
- Margriet Oosterveld
- Canisius Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands
- Thomas Pabst
- Inselspital, University Hospital, 3010 Bern, Switzerland
- Marjolein van der Poel
- Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
- Harm Sinnige
- Jeroen Bosch Ziekenhuis, 5223 GZ Den Bosch, The Netherlands
- Olivier Spertini
- Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
- Wim Terpstra
- OLVG, 1091 AC Amsterdam, The Netherlands
- Lidwine Tick
- Maxima Medical Center, 5631 BM Eindhoven, The Netherlands
- Walter van der Velden
- Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Marie-Christiane Vekemans
- Hopital St. Luc, 1200 Brussels, Belgium
- Edo Vellenga
- University Medical Center, 9713 GZ Groningen, The Netherlands
- Okke de Weerdt
- Antonius Hospital, 3435 CM Nieuwegein, The Netherlands
- Peter Westerweel
- Albert Schweitzer Hospital, 3318 AT Dordrecht, The Netherlands
- Georg Stüssi
- Istituto Oncologico Della Svizzera Italiana, 6500 Bellinzona, Switzerland
- Yvette van Norden
- Hovon Data Center, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
- Gert Ossenkoppele
- Amsterdam University Medical Centers, loc. VUmc, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- DOI
- https://doi.org/10.3390/cancers13040672
- Journal volume & issue
-
Vol. 13,
no. 4
p. 672
Abstract
Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients.
Keywords