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- Title
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.
- Authors
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
- Abstract
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.
- Subjects
CANCER treatment; ACUTE myeloid leukemia; ARSENIC trioxide; EVALUATION of clinical trials; COMPARATIVE studies
- Publication
Cancer (0008543X), 2011, Vol 117, Issue 21, p4831
- ISSN
0008-543X
- Publication type
Article
- DOI
10.1002/cncr.26097