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Article Dans Une Revue Leukemia Année : 2013

A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse.

S. Park
  • Fonction : Auteur
N. Chapuis
  • Fonction : Auteur
Franck Saint-Marcoux
  • Fonction : Auteur
  • PersonId : 910468
C. Recher
  • Fonction : Auteur
T. Prebet
  • Fonction : Auteur
J.-Y. Cahn
  • Fonction : Auteur
T. Leguay
  • Fonction : Auteur
P. Bories
  • Fonction : Auteur
F. Witz
  • Fonction : Auteur
T. Lamy
  • Fonction : Auteur
P. Mayeux
  • Fonction : Auteur
J. Tamburini
  • Fonction : Auteur
A. Merlat
  • Fonction : Auteur
R. Delepine
  • Fonction : Auteur
N. Vey
  • Fonction : Auteur
M. C. Béné
  • Fonction : Auteur
N. Ifrah
  • Fonction : Auteur
D. Bouscary
  • Fonction : Auteur

Résumé

The mTORC1 signaling pathway is constitutively activated in almost all acute myelogenous leukemia (AML) patients. We conducted a phase Ib trial combining RAD001 (everolimus), an allosteric inhibitor of mTORC1, and conventional chemotherapy, in AML patients under 65 years of age at first relapse (clinical trial NCT 01074086). Increasing doses of RAD001 from 10-70 mg were administrated orally on days 1 and 7 (d1 and d7) of a 3+7 daunorubicin+cytarabine conventional induction chemotherapy regimen. Twenty-eight patients were enrolled in this trial. The treatment was well tolerated with <10% toxicity, mainly involving the gastrointestinal tract and lungs. In this phase Ib trial, the RAD001 maximum tolerated dose was not reached at 70 mg. Sixty-eight percent of patients achieved CR, of which 14 received a double induction. Eight subsequently were intensified with allogeneic-stem cell transplant. Strong plasma inhibition of P-p70S6K was observed after RAD001 administration, still detectable at d7 (d7)at the 70 mg dosage. CR rates in patients with RAD001 areas under or above the curve median were 53% versus 85%. A 70 mg dose of RAD001 at d1 and d7 of an induction chemotherapy regimen for AML has acceptable toxicity and may improve treatment.

Domaines

Cancer
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Dates et versions

hal-00849677 , version 1 (31-07-2013)

Identifiants

Citer

S. Park, N. Chapuis, Franck Saint-Marcoux, C. Recher, T. Prebet, et al.. A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse.. Leukemia, 2013, 27 (7), pp.1479-86. ⟨10.1038/leu.2013.17⟩. ⟨hal-00849677⟩
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