Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS
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
(2021) Cancers, volume 13, issue 4
(Article)
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
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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.
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Keywords: Aminopeptidase inhibitor, AML, Clinical trial, Elderly, High-risk MDS, Tosedostat, Oncology, Cancer Research, Journal Article
ISSN: 2072-6694
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: Funding: Dutch Cancer Foundation for financial support; Chroma Therapeutics for financial support and delivery of drug for free. Funding Information: Dutch Cancer Foundation for financial support; Chroma Therapeutics for financial support and delivery of drug for free. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
(Peer reviewed)