Phase II Study of Low-Dose Decitabine for the Front-Line Treatment of Older Patients with Acute Myeloid Leukemia (AML).

Decitabine (Dacogen™) was recently approved for the treatment of patients with myelodysplastic syndromes (MDS). Response in MDS is associated with reversal of the hypermethylated phenotype of silenced genes. The prevalence of hypermethylated genes contributing to AML progression, coupled with the challenges involved in the treatment of AML in the elderly, is a basis for exploring the activity of decitabine in this patient population. The objective of this phase II trial was to estimate the rate of morphologic complete response (CR) in patients with AML. To be eligible for the study, patients had to be at least 60 years old with newly diagnosed, untreated AML with intermediate- or poor-risk cytogenetics, and they could not be candidates for standard induction chemotherapy. Decitabine was given at a dose of 20 mg/m² over 1 hour for 5 consecutive days every 4 weeks. At the time of the analysis, 27 patients were enrolled in the trial (14 men, 13 women; median age = 69 years, range = 61–87) and received at least 1 cycle of treatment (median = 4, range = 1–10). Seventeen patients (63%) received 3 or more cycles of treatment. Seven of 27 patients (26%) responded, 2 patients (7%) with a morphologic CR, 1 patient (4%) with a complete cytogenetic response (CRc), and 4 patients (15%) with a morphologic CR with incomplete blood count recovery (CRi) according to AML response criteria (Cheson, JCO 2003). In addition to these defined responses, 11 other patients demonstrated clinical benefit by achieving stable disease, with 4 of these patients having a >25% reduction in bone marrow blasts. Median time to response was 3 treatment cycles. Of the 13 patients with a prior history of MDS, 6 patients had a response (CR, CRc, or CRi, 46%). Two of 2 patients with leukemia cutis exhibited complete resolution of skin lesions and responded (CR or CRi). Eight patients discontinued treatment prior to receiving 3 cycles because of death, progressive disease, or patient decision. All patients were evaluated for safety. Besides myelosuppression, the most commonly reported adverse events considered related to decitabine treatment were fatigue, nausea, febrile neutropenia, vomiting, and asthenia. Decitabine given daily for 5 days showed activity in patients with newly diagnosed AML, with a toxicity profile that was manageable in this older patient population. The results to date are comparable to those from previous studies in AML patients using a variety of decitabine schedules, which have reported CR rates from 14% to 33% (