@article{8710993,
  abstract     = {{Simple Summary Treatment results of acute myeloid leukemia (AML) in elderly patients are unsatisfactory. We investigated in an open label randomized phase II study whether addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy would improve outcome in this population. 231 AML patients > 65 years of age were randomly assigned to receive standard chemotherapy with or without tosedostat for two cycles. We found that complete bone marrow leukemia clearance was not significantly different between both arms. After two years, survival was 33% for the standard arm versus 18% for the tosedostat arm. More patients died due to infectious complications in the tosedostat arm than after standard treatment. Also, a cardiac rhythm abnormality called atrial fibrillation was more often seen in the tosedostat arm. We conclude that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly patients with acute myeloid leukemia. 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/m(2) 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.}},
  articleno    = {{672}},
  author       = {{Janssen, Jeroen and Lowenberg, Bob and Manz, Markus and Bargetzi, Mario and Biemond, Bart and Borne, Peter von Dem and Breems, Dimitri and Brouwer, Rolf and Chalandon, Yves and Deeren, Dries and Efthymiou, Anna and Gjertsen, Bjorn-Tore and Graux, Carlos and Gregor, Michael and Heim, Dominik and Hess, Urs and Hoogendoorn, Mels and Jaspers, Aurelie and Jie, Asiong and Jongen-Lavrencic, Mojca and Klein, Saskia and van der Klift, Marjolein and Kuball, Jurgen and van Lammeren-Venema, Danielle and Legdeur, Marie-Cecile and van de Loosdrecht, Arjan and Maertens, Johan and Kooy, Marinus van Marwijk and Moors, Ine and Nijziel, Marten and van Obbergh, Florence and Oosterveld, Margriet and Pabst, Thomas and van der Poel, Marjolein and Sinnige, Harm and Spertini, Olivier and Terpstra, Wim and Tick, Lidwine and van der Velden, Walter and Vekemans, Marie-Christiane and Vellenga, Edo and de Weerdt, Okke and Westerweel, Peter and Stussi, Georg and van Norden, Yvette and Ossenkoppele, Gert}},
  issn         = {{2072-6694}},
  journal      = {{CANCERS}},
  keywords     = {{AML,high-risk MDS,tosedostat,clinical trial,aminopeptidase,inhibitor,elderly}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{11}},
  title        = {{Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with AML and high risk MDS}},
  url          = {{http://dx.doi.org/10.3390/cancers13040672}},
  volume       = {{13}},
  year         = {{2021}},
}

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