CI-994 (N-acetyl-dinaline) in combination with conventional anti-cancer agents is effective against acute myeloid leukemia in vitro and in vivo.
N-acetyl-dinaline (CI-994) is an investigational anti-cancer drug which inhibits histone deacetylases. We evaluated the interaction between CI-994 and conventional chemotherapeutics used in acute myeloid leukemia (AML) in a rat model for AML and Brown Norway rat acute myelocytic leukemia (BNML). In vitro, CI-994 in combination with cytarabine (ara-C), daunorubicin and mitoxantrone, resulted in moderate synergism. In vivo, higher dosages of CI-994 induced complete remissions. CI-994/ara-C was very active against BNML. The combinations of CI-994/daunorubicin and CI-994/mitoxantrone were also active against BNML. This study demonstrates favorable in vitro and in vivo interactions between CI-994 and conventional anti-cancer agents used for the treatment of AML.
Hubeek
I
I
Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands. isabelle.hubeek@vumc.nl
Comijn
E M
EM
Van der Wilt
C L
CL
Merriman
R L
RL
Padron
J M
JM
Kaspers
G J L
GJ
Peters
G J
GJ
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D001772:Blood Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D010655:Phenylenediamines / Q000008:administration & dosage*; D051381:Rats; D011914:Rats, Inbred BN
D001549:Benzamides; D010655:Phenylenediamines; D003561:Cytarabine; D008942:Mitoxantrone; C081895:tacedinaline; D003630:Daunorubicin