Author(s): Blum W, Garzon R, Klisovic RB, Schwind S, Walker A,
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Abstract A phase II clinical trial with single-agent decitabine was conducted in older patients (>or=60 years) with previously untreated acute myeloid leukemia (AML) who were not candidates for or who refused intensive chemotherapy. Subjects received low-dose decitabine at 20 mg/m(2) i.v. over 1 h on days 1 to 10. Fifty-three subjects enrolled with a median age of 74 years (range, 60-85). Nineteen (36\%) had antecedent hematologic disorder or therapy-related AML; 16 had complex karyotypes (>or=3 abnormalities). The complete remission rate was 47\% (n = 25), achieved after a median of three cycles of therapy. Nine additional subjects had no morphologic evidence of disease with incomplete count recovery, for an overall response rate of 64\% (n = 34). Complete remission was achieved in 52\% of subjects presenting with normal karyotype and in 50\% of those with complex karyotypes. Median overall and disease-free survival durations were 55 and 46 weeks, respectively. Death within 30 days of initiation of treatment occurred in one subject (2\%), death within 8 weeks in 15\% of subjects. Given the DNA hypomethylating effect of decitabine, we examined the relationship of clinical response and pretreatment level of miR-29b, previously shown to target DNA methyltransferases. Higher levels of miR-29b were associated with clinical response (P = 0.02). In conclusion, this schedule of decitabine was highly active and well tolerated in this poor-risk cohort of older AML patients. Levels of miR-29b should be validated as a predictive factor for stratification of older AML patients to decitabine treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT00492401.
This article was published in Proc Natl Acad Sci U S A
and referenced in Journal of Pharmacogenomics & Pharmacoproteomics