Decitabine improves patient outcomes in myelodysplastic syndromes - Resuits of a Phase III randomized study

被引:1196
作者
Kantarjian, H
Issa, JPJ
Rosenfeld, CS
Bennett, JM
Albitar, M
DiPersio, J
Klimek, V
Slack, J
de Castro, C
Ravandi, F
Helmer, R
Shen, LL
Nimer, SD
Leavitt, R
Raza, A
Saba, H
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
[2] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14627 USA
[3] Quest Diagnost, Nichols Inst, San Juan Capistrano, CA USA
[4] Washington Univ, Sch Med, St Louis, MO USA
[5] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA
[6] Roswell Pk Canc Inst, Buffalo, NY 14263 USA
[7] Duke Univ, Med Ctr, Durham, NC USA
[8] Univ Illinois, Chicago, IL USA
[9] SW Reg Canc Ctr, Austin, TX USA
[10] Pharma Pacific Inc, Woodside, CA USA
[11] Rush Presbyterian St Lukes Med Ctr, Chicago, IL USA
[12] James A Haley Vet Hosp, Tampa, FL USA
[13] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA
关键词
decitabine; azacitidine; myelodysplastic syndrome; acute myelogenous leukemia; hypomethylating;
D O I
10.1002/cncr.21792
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. Aberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters. METHODS. A total of 170 patients with MDS were randomized to receive either decitabine at a dose of 15 mg/m(2) given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m(2) per Course) and repeated every 6 weeks, or best supportive care. Response was assessed using the International Working Group criteria and required that response criteria be met for at least 8 weeks. RESULTS. Patients who were treated with decitabine achieved a significantly higher overall response rate (17%), including 9% complete responses, compared with supportive care (0%) (P <.001). An additional 12 patients who were treated with decitabine (13%) achieved hematologic improvement. Responses were durable (median, 10.3 mos) and were associated with transfusion independence. Patients treated with decitabine had a trend toward a longer median time to acute myelogenous leukemia (AML) progression or death compared with patients who received supportive care alone (all patients, 12.1 mos vs. 7.8 mos [P = 0.16]; those with International Prognostic Scoring System intermediate-2/high-risk disease, 12.0 mos vs. 6.8 mos [P = 0.03]; those with de novo disease, 12.6 mos vs. 9.4 mos [P = 0.04]; and treatment-naive patients, 12.3 mos vs. 7.3 mos [P = 0.08]). CONCLUSIONS. Decitabine was found to be clinically effective in the treatment of patients with MDS, provided durable responses, and improved time to AML transformation or death. The duration of decitabine therapy may improve these results further.
引用
收藏
页码:1794 / 1803
页数:10
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