Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia

Kantarjian H.M.Thomas X.G.Dmoszynska A.Wierzbowska A.Mazur G.Mayer J.Gau J.-P.WEN-CHIEN CHOUBuckstein R.Cermak J.Kuo C.-Y.Oriol A.Ravandi F.Faderl S.Delaunay J.Lys?k D.Minden M.Arthur C.2021-02-052021-02-0520120732-183Xhttps://scholars.lib.ntu.edu.tw/handle/123456789/548704Purpose: This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics.Patients and Methods: Patients (N = 485) age ? 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m2 per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded.Results: The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%).Conclusion: In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis. ? 2012 by American Society of Clinical Oncology.[SDGs]SDG35 aza 2' deoxycytidine; cytarabine; acute granulocytic leukemia; aged; anemia; article; bronchopneumonia; cancer survival; controlled study; drug efficacy; drug fever; drug safety; drug withdrawal; dyspnea; febrile neutropenia; female; follow up; human; hypokalemia; leukemia remission; leukopenia; low drug dose; major clinical study; male; multicenter study; multiple cycle treatment; neutropenia; overall survival; patient compliance; phase 3 clinical trial; pneumonia; priority journal; randomized controlled trial; sepsis; thrombocytopenia; treatment response; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Azacitidine; Choice Behavior; Cytarabine; Decision Making; Drug Administration Schedule; Female; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Neutropenia; Palliative Care; Patient Participation; Remission Induction; Risk Assessment; Risk Factors; Thrombocytopenia; Treatment OutcomeMulticenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemiajournal article10.1200/JCO.2011.38.9429226898052-s2.0-84864063679