Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a phase III randomized study

Hagop Kantarjlan, Jean Pierre J Issa, Craig S. Rosenfeld, John M. Bennett, Maher Albitar, John DiPersio, Virginia Klimek, James Slack, Carlos De Castro, Farhad Ravandi, Richard Helmer, Lanlan Shen, Stephen D Nimer, Richard Leavitt, Azra Raza, Hussain Saba

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Abstract

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/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 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.

Original languageEnglish
Pages (from-to)1794-1803
Number of pages10
JournalCancer
Volume106
Issue number8
DOIs
StatePublished - May 15 2006
Externally publishedYes

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decitabine
Myelodysplastic Syndromes
Acute Myeloid Leukemia
DNA Methylation
Therapeutics

Keywords

  • Acute myelogenous leukemia
  • Azacitidine
  • Decitabine
  • Hypomethylating
  • Myelodysplastic syndrome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kantarjlan, H., Issa, J. P. J., Rosenfeld, C. S., Bennett, J. M., Albitar, M., DiPersio, J., ... Saba, H. (2006). Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a phase III randomized study. Cancer, 106(8), 1794-1803. https://doi.org/10.1002/cncr.21792

Decitabine improves patient outcomes in myelodysplastic syndromes : Results of a phase III randomized study. / Kantarjlan, Hagop; Issa, Jean Pierre J; Rosenfeld, Craig S.; Bennett, John M.; Albitar, Maher; DiPersio, John; Klimek, Virginia; Slack, James; De Castro, Carlos; Ravandi, Farhad; Helmer, Richard; Shen, Lanlan; Nimer, Stephen D; Leavitt, Richard; Raza, Azra; Saba, Hussain.

In: Cancer, Vol. 106, No. 8, 15.05.2006, p. 1794-1803.

Research output: Contribution to journalArticle

Kantarjlan, H, Issa, JPJ, Rosenfeld, CS, Bennett, JM, Albitar, M, DiPersio, J, Klimek, V, Slack, J, De Castro, C, Ravandi, F, Helmer, R, Shen, L, Nimer, SD, Leavitt, R, Raza, A & Saba, H 2006, 'Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a phase III randomized study', Cancer, vol. 106, no. 8, pp. 1794-1803. https://doi.org/10.1002/cncr.21792
Kantarjlan H, Issa JPJ, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J et al. Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a phase III randomized study. Cancer. 2006 May 15;106(8):1794-1803. https://doi.org/10.1002/cncr.21792
Kantarjlan, Hagop ; Issa, Jean Pierre J ; Rosenfeld, Craig S. ; Bennett, John M. ; Albitar, Maher ; DiPersio, John ; Klimek, Virginia ; Slack, James ; De Castro, Carlos ; Ravandi, Farhad ; Helmer, Richard ; Shen, Lanlan ; Nimer, Stephen D ; Leavitt, Richard ; Raza, Azra ; Saba, Hussain. / Decitabine improves patient outcomes in myelodysplastic syndromes : Results of a phase III randomized study. In: Cancer. 2006 ; Vol. 106, No. 8. pp. 1794-1803.
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abstract = "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/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 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.",
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AU - Issa, Jean Pierre J

AU - Rosenfeld, Craig S.

AU - Bennett, John M.

AU - Albitar, Maher

AU - DiPersio, John

AU - Klimek, Virginia

AU - Slack, James

AU - De Castro, Carlos

AU - Ravandi, Farhad

AU - Helmer, Richard

AU - Shen, Lanlan

AU - Nimer, Stephen D

AU - Leavitt, Richard

AU - Raza, Azra

AU - Saba, Hussain

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N2 - 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/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 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.

AB - 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/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 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.

KW - Acute myelogenous leukemia

KW - Azacitidine

KW - Decitabine

KW - Hypomethylating

KW - Myelodysplastic syndrome

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