Pharmacokinetic evaluation of decitabine for the treatment of leukemia

Bryan, Jeffrey C.; Kantarjian, Hagop; Jabbour, Elias

doi:10.1517/17425255.2011.575062

Cited by 21 publications

(13 citation statements)

References 81 publications

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“…The development of hypomethylating agents provides an alternative treatment strategy [19–28]. This meta-analysis showed that decitabine brought considerable treatment response in elderly AML patients.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of decitabine in treatment of elderly patients with acute myeloid leukemia: A systematic review and meta-analysis

Zhou

Yao

et al. 2017

Oncotarget

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Elderly patients with acute myeloid leukemia (AML) have limited treatment options concerned about their overall fitness and potential treatment related mortality. Although a number of clinical trials demonstrated benefits of decitabine treatment in elderly AML patients, the results remains controversial. A meta-analysis was performed to evaluate efficacy and safety of decitabine in treatment of elderly AML patients. Eligible studies were identified from PubMed, Web of Science, Embase and Cochrane Library. Nine published studies were included in the meta-analysis, enrolling 718 elderly AML patients. The efficacy outcomes were complete remission (CR), overall response rate (ORR) and overall survival (OS). Safety was evaluated based on treatment related grades 3–4 adverse events (AEs) and early death (ED) rate. Pooled estimates with 95% confidence interval (CI) for CR, ORR and OS were 27% (95% CI 19%–36%), 37% (95% CI 28%–47%) and 8.09 months (95% CI 5.77–10.41), respectively. The estimated treatment related early death (ED) incidences were within 30-days 7% (95% CI 2%–11%) and 60-days 17% (95% CI 11%–22%), respectively. Thrombocytopenia was the most common grades 3–4 AEs. Subgroup analyses of age, cytogenetics risk, AML type and bone marrow blast percentage showed no significant differences of treatment response to decitabine. In conclusion, decitabine is an effective and well-tolerated therapeutic alternative with acceptable side effects in elderly AML patients.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of decitabine in treatment of elderly patients with acute myeloid leukemia: A systematic review and meta-analysis

Zhou

Yao

et al. 2017

Oncotarget

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“…The DNA methylation inhibitors, AZA and DAC, have been approved by the FDA for the treatment of MDS and AML (Jones & Taylor, 1980;Jones et al, 1982;Santi et al, 1984;Cheng et al, 2004;Bryan et al, 2011;Lübbert, 2000;Robak, 2011). As a side-effect, AZA and DAC can incorporate into the genome as part of its mechanism of action, which can cause mutations in the daughter cells if the cell does not die (Jones & Taylor, 1980;Santi et al, 1984;Davidson et al, 1992).…”

Section: Nucleosidic Dna Methylation Inhibitorsmentioning

confidence: 99%

Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

Liu

Lau

et al. 2015

Pharmacology & Therapeutics

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“…It leads to DNMT depletion and genome hypomethylation. Toxic at high doses, decitabine is well tolerated at lower doses [132]. Recently, a study shows lower toxicity of a derivative of decitabine, the 2′-deoxy-5,6-dihydro-5-azacytidine at doses that induce similar DNA hypomethylation and gene reactivation [133].…”

Section: Current Drugs/dna Methylation Inhibitors and Clinical Trimentioning

confidence: 99%

DNA Methylation and Cancer Diagnosis

Delpu

Cordelier

Cho

et al. 2013

IJMS

138

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DNA methylation is a major epigenetic modification that is strongly involved in the physiological control of genome expression. DNA methylation patterns are largely modified in cancer cells and can therefore be used to distinguish cancer cells from normal tissues. This review describes the main technologies available for the detection and the discovery of aberrantly methylated DNA patterns. It also presents the different sources of biological samples suitable for DNA methylation studies. We discuss the interest and perspectives on the use of DNA methylation measurements for cancer diagnosis through examples of methylated genes commonly documented in the literature. The discussion leads to our consideration for why DNA methylation is not commonly used in clinical practice through an examination of the main requirements that constitute a reliable biomarker. Finally, we describe the main DNA methylation inhibitors currently used in clinical trials and those that exhibit promising results.

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Pharmacokinetic evaluation of decitabine for the treatment of leukemia

Cited by 21 publications

References 81 publications

Efficacy and safety of decitabine in treatment of elderly patients with acute myeloid leukemia: A systematic review and meta-analysis

Efficacy and safety of decitabine in treatment of elderly patients with acute myeloid leukemia: A systematic review and meta-analysis

Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

DNA Methylation and Cancer Diagnosis

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