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

  title={Results of decitabine (5‐aza‐2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia},
  author={Hagop M. Kantarjian and Susan O'brien and Jorge E. Cortes and Francis J. Giles and Stefan H. Faderl and Jean-Pierre J. Issa and Guillermo Garcia-Manero and Mary Beth Rios and Jianqin Shan and Michael Andreeff and Michael J. Keating and Moshe Talpaz},
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. 

Decitabine in chronic leukemias.

There is clear evidence of molecular (hypomethylation) as well as hematologic and cytogenetic responses to decitabine in chronic myelogenous leukemia of all phases, including in patients resistant to imatinib mesylate.

Phase II study of low‐dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia

A Phase II study was performed on low‐dose decitabine, a DNA methyltransferase inhibitor, in combination with imatinib in patients with CML in accelerated phase (AP) and myeloid blastic phase (BP).

Epigenetic therapy with decitabine for myelodysplasia and leukemia.

An overview of Decitabine with regard to the chemistry, pharmacokinetics and the data that support its role as the new therapeutic agent in leukemia and myelodysplastic syndrome is presented.

Decitabine improves patient outcomes in myelodysplastic syndromes

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

Decitabine: a historical review of the development of an epigenetic drug

The use of decitabine in MDS, AML, CML, stem cell transplant, sickle cell anemia and thalassemia looks promising, and the epigenetic dose seems lower than the cytotoxic dose.

Decitabine: a historical review of the development of an epigenetic drug

The use of decitabine in MDS, AML, CML, stem cell transplant, sickle cell anemia and thalassemia looks promising, and the epigenetic dose seems lower than the cytotoxic dose.

Demethylating agents in myeloid malignancies

Demethylating agents are the standard of care for patients with higher risk MDS and the only agent known to improve the natural history of MDS.

The use of hypomethylating agents in the treatment of hematologic malignancies

Postulated to work through hypomethylation of DNA causing induction of gene expression, the precise mechanism of action of these agents is not yet clear but future studies are likely to combine these agents with other drugs like the histone deacetylase inhibitors that act in related pathways.

Pharmacokinetic and pharmacodynamic analysis of 5-aza-2’-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy

Based on analyses of preclinical and clinical data, low dose 5-AZA-CdR has the potential to be an effective form of therapy in some patients with cancer and novel dose schedules are proposed for investigation in patients withcancer.

Importance of dose-schedule of 5-aza-2'-deoxycytidine for epigenetic therapy of cancer

It is shown that intensification of the DAC dose markedly increased its antineoplastic activity in mouse models of cancer, and there is a good correlation between the concentrations of DAC that reduce in vitro clonogenicity, reactivate TSGs and inhibit DNA methylation.



Pilot study of 5-aza-2'-deoxycytidine (Decitabine) in the treatment of poor prognosis acute myelogenous leukemia patients: preliminary results.

It is suggested that Decitabine may have a prominent role in the treatment of those AML patients with poor general conditions and/or advanced age, as shown by the kinetic of remission and immunotyping studies.

Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies.

It is concluded that decitabine is effective in myeloid malignancies, and low doses are as or more effective than higher doses.

Results of decitabine therapy in the accelerated and blastic phases of chronic myelogenous leukemia

Decitabine has promising activity in CML and may show activity in other myeloid disorders such as acuteMyeloid leukemia and myelodysplastic syndrome, as well as in other hematologic malignancies, alone or with other drug combinations.

5-Aza-2'-deoxycytidine (Decitabine) induces trilineage response in unfavourable myelodysplastic syndromes.

Decitabine is able to induce trilineage hematological responses in advanced MDS patients along with a stable normalization of the PB and BM picture in some of the subjects, which deserves careful investigation in this heterogeneous group of disorders.

The antileukaemic activity of 5-Aza-2 deoxycytidine (Aza-dC) in patients with relapsed and resistant leukaemia.

It is demonstrated that Aza-dC in combination with Amsacrine has major antileukaemic properties in patients who have not already received extensive Ara-C therapy and is therefore better tolerated.

Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase.

Imatinib mesylate therapy was less toxic and produced a higher response rate, longer median survival, and lower 4-week induction mortality than standard cytarabine-based therapy, and is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients.

It is confirmed that DAC therapy was effective in half of the studied patients with high-risk myelodysplastic syndrome and is especially active in the patients with the worst prognoses.

Preliminary results with 5-aza-2'-deoxycytidine (DAC)-containing chemotherapy in patients with relapsed or refractory acute leukemia. The EORTC Leukemia Cooperative Group.

DAC is an anti-leukemic agent, comparable to high dose Ara-C with comparable severe toxicity, and achieves a complete remission in patients with acute relapsed leukemia.

Response to therapy is independently associated with survival prolongation in chronic myelogenous leukemia in the blastic phase

The purpose of this study was to analyze the effect of response in CML‐BP on survival prolongation and to propose a new treatment strategy based on response analyses.

Methylation of the ABL1 promoter in chronic myelogenous leukemia: lack of prognostic significance.

Pa methylation in CML is associated with disease progression but does not appear to predict for survival or response to interferon-based therapy.