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Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS

Contributors

Janssen, Jeroen; Löwenberg, Bob; Manz, Markus; Bargetzi, Mario; Biemond, Bart; Borne, Peter von dem; Breems, Dimitri; Brouwer, Rolf; Chalandon, Yves; Deeren, Dries; Efthymiou, Anna; Gjertsen, Bjørn-Tore; Graux, Carlos; Gregor, Michael; Heim, Dominik; Hess, Urs; Hoogendoorn, Mels; Jaspers, Aurelie; Jie, Asiong; Jongen-Lavrencic, Mojca; Klein, Saskia; Klift, Marjolein van der; Kuball, Jürgen; Lammeren-Venema, Danielle van; Legdeur, Marie-Cecile; Loosdrecht, Arjan van de; Maertens, Johan; Kooy, Marinus van Marwijk; Moors, Ine; Nijziel, Marten; Obbergh, Florence van; Oosterveld, Margriet; Pabst, Thomas; Poel, Marjolein van der; Sinnige, Harm; Spertini, Olivier; Terpstra, Wim; Tick, Lidwine; Velden, Walter van der; Vekemans, Marie-Christiane; Vellenga, Edo; Weerdt, Okke de; Westerweel, Peter; Stüssi, Georg; Norden, Yvette van; Ossenkoppele, Gert

Published in

Cancers, vol. 13, no. 4, 672

Publication date

2021-02-07

First online date

2021-02-07

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/m2twice 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

  • AML
  • Aminopeptidase inhibitor
  • Clinical trial
  • Elderly
  • High-risk MDS
  • Tosedostat

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

JANSSEN, Jeroen et al. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS. In: Cancers, 2021, vol. 13, n° 4, p. 672. doi: 10.3390/cancers13040672

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Article (Published version)
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Identifiers

Additional URL for this publication

https://www.mdpi.com/2072-6694/13/4/672

Journal ISSN

2072-6694
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Technical informations

Creation

21/10/2021 08:14:00

First validation

21/10/2021 08:14:00

Update

16/03/2023 02:41:48

Status update

16/03/2023 02:41:44

Last indexation

19/11/2024 15:04:30
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