Premium
Phase 1 study of arsenic trioxide, high‐dose cytarabine, and idarubicin to down‐regulate constitutive signal transducer and activator of transcription 3 activity in patients aged <60 years with acute myeloid leukemia
Author(s) -
Wetzler Meir,
Andrews Chris,
Ford Laurie A.,
Tighe Sheila,
Barcos Maurice,
Sait Sheila N. J.,
Block AnneMarie W.,
Nowak Norma J.,
Baer Maria R.,
Wang Eunice S.,
Baumann Heinz
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26097
Subject(s) - medicine , cytarabine , idarubicin , myeloid leukemia , oncology , adverse effect , pharmacology , arsenic trioxide , gastroenterology , apoptosis , biology , biochemistry
BACKGROUND: Constitutive activation of signal transducer and activator of transcription‐3 (STAT3) was detected in blasts from approximately 50% of patients with acute myeloid leukemia (AML) and was correlated with an adverse outcome. In vitro treatment of AML blasts with arsenic trioxide (ATO) down‐regulated STAT3 activity within 6 hours associated with a reduced viability within 48 hours. METHODS: A phase 1 clinical trial to evaluate the biologically effective dose and/or the maximally tolerated dose (MTD) of ATO in vivo in conjunction with high‐dose cytarabine (Hidac) and idarubicin (Ida) in patients with AML aged <60 years was conducted. Data were compared with 117 historic AML patients who had received treatment with Hidac/Ida. RESULTS: In total, 61 patients were enrolled onto 11 different dose levels (from 0.01 to 0.65 mg/kg ideal body weight). The MTD was 0.5 mg/kg. Compared with historic controls, patients who received ATO/Hidac/Ida, although they had similar pretreatment characteristics, had better overall survival ( P = .039). CONCLUSIONS: ATO priming may have improved the outcome of patients aged <60 years with AML who received Hidac/Ida. The current data suggested that ATO may enhance the effect of chemotherapy. The authors concluded that further studies of this novel combination are warranted. Cancer 2011;. © 2011 American Cancer Society.