Methods of treating leukemia with suberoylanilide hydroxamic...

A - Human Necessities – 61 – K

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A61K 31/19 (2006.01)

Patent

CA 2543319

The present invention relates to methods of treating cancers, e.g., leukemia. More specifically, the present invention relates to methods of treating acute and chronic leukemias including Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML), Chronic Lymphocytic leukemia (CLL), Chronic myeloid leukemia (CML) and Hairy Cell Leukemia, by administration of pharmaceutical compositions comprising HDAC inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The oral formulations of the pharmaceutical compositions have favorable pharmacokinetic profiles such as high bioavailability and surprisingly give rise to high blond levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

La présente invention concerne des procédés permettant de traiter des cancers, et notamment la leucémie. L'invention concerne plus particulièrement le traitement de leucémies aiguës et chroniques telles que la leucémie lymphoïde aiguë, de la leucémie myéloïde aiguë, de la leucémie lymphoïde chronique et de la leucémie myéloïde chronique. Un tel traitement nécessite l'administration de compositions pharmaceutiques comprenant des inhibiteurs de l'histone déacétylase (HDAC) tels que l'acide hydroxamique suberoylanilide (SAHA). Les formulations orales de ces compositions pharmaceutiques présentent des profils pharmacocinétiques favorables tels qu'une bio-disponibilité élevée, et une persistance importante, à niveau élevé et de façon prolongée, des composés actifs dans le sang. L'invention concerne également une posologie quotidienne sans risques de ces compositions pharmaceutiques, facile à suivre, et qui donne in vivo une quantité thérapeutiquement efficace d'inhibiteurs de la HDAC.

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