Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia

Hagop M. Kantarjian, Susan O'Brien, Jorge Cortes, Francis J. Giles, Stefan Faderl, Jean Pierre Issa, Guillermo Garcia-Manero, Mary Beth Rios, Jianqin Shan, Michael Andreeff, Michael Keating, Moshe Talpaz

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187 Scopus citations

Abstract

BACKGROUND. General and site-specific DNA methylation is associated with tumor progression and resistance in several cancers, including chronic myelogenous leukemia (CML). Decitabine is a hypomethylating agent that has shown encouraging preliminary anti-CML activity. This study evaluated the activity and toxicity of decitabine in different phases of CML. METHODS. One hundred and thirty patients with CML were treated: 123 with Philadelphia chromosome (Ph)-positive CML (64 blastic, 51 accelerated, 8 chronic) and 7 with Ph-negative CML. Decitabine was given at 100 mg/m2 over 6 hours every 12 hours × 5 days (1000 mg/m2 per course) in the first 13 patients, 75 mg/m2 in the subsequent 33 patients, and 50 mg/m2 in the remaining 84 patients. RESULTS. A total of 552 courses were given to the 130 patients. Only four patients (3%) died during the first course from myelosuppressive complications (three patients) or progressive disease (one patient). Of 64 patients in the CML blastic phase, 18 patients (28%) achieved objective responses. Of these 18 patients, 6 achieved complete hematologic responses (CHR), 2 achieved partial hematologic responses (PHR), 7 achieved hematologic improvements (HI), and 3 returned to the second chronic phase (second CP). Five patients (8%) had cytogenetic responses. Among 51 patients in the accelerated phase, 28 patients (55%) achieved objective responses (12 CHR, 10 PHR, 3 HI, and 3 second CP). Seven patients (14%) had cytogenetic responses. Among eight patients treated in the chronic phase, five (63%) had objective responses. Of seven patients treated for Ph-negative CML, four (57%) had objective responses. There was no evidence of a dose-response effect. The estimated 3-year survival rate was less than 5% in the blastic phase and 27% in the accelerated phase. The only significant toxicity reported was severe myelosuppression, which was delayed, prolonged, and dose dependent. With decitabine 50-75 mg/m2, the median time to granulocyte recovery above 0.5 × 109/L was about 4 weeks. Myelosuppression-associated complications included febrile episodes in 37% and documented infections in 34%. CONCLUSIONS. Decitabine appears to have significant anti-CML activity. Future studies should evaluate lower-dose, longer-exposure decitabine schedules alone in imatinib-resistant CML, as well as combinations of decitabine and imatinib in different CML phases.

Original languageEnglish (US)
Pages (from-to)522-528
Number of pages7
JournalCancer
Volume98
Issue number3
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Keywords

  • Chronic myelogenous leukemia
  • Decitabine
  • Myelosuppressive complications
  • Response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Kantarjian, H. M., O'Brien, S., Cortes, J., Giles, F. J., Faderl, S., Issa, J. P., Garcia-Manero, G., Rios, M. B., Shan, J., Andreeff, M., Keating, M., & Talpaz, M. (2003). Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. Cancer, 98(3), 522-528. https://doi.org/10.1002/cncr.11543