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Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitidine.

ABSTRACT: Azacitidine and decitabine are the two hypomethylating agents approved by the Food and Drug Administration for the treatment of patients with myelodysplastic syndrome (MDS). The efficacy of one agent post-failure of the other is unknown. Fourteen patients with MDS post-azacitidine failure/lack of response/intolerance were treated with decitabine. Overall three patients achieved a complete remission, and one patient had hematologic improvement, for an overall response rate of 28%. Of the responders, one stopped prior 5-azacitidine owing to disease progression, two for no response and one for severe skin toxicity. Grade 3-4 drug related side-effects were minimal. Global methylation studies in patient samples showed decrease of methylation after treatment with decitabine. As in our previous studies, there was no difference in hypomethylation between responders and nonresponders. We conclude that clinically significant responses with decitabine can be seen in patients post-azacitidine failure without significant toxicity.

SUBMITTER: Borthakur G

PROVIDER: S-EPMC3702160 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitidine.

Borthakur Gautam G Ahdab Samih El SE Ravandi Farhad F Faderl Stefan S Ferrajoli Alessandra A Newman Beth B Issa Jean-Pierre JP Kantarjian Hagop H

Leukemia & lymphoma 20080401 4

Azacitidine and decitabine are the two hypomethylating agents approved by the Food and Drug Administration for the treatment of patients with myelodysplastic syndrome (MDS). The efficacy of one agent post-failure of the other is unknown. Fourteen patients with MDS post-azacitidine failure/lack of response/intolerance were treated with decitabine. Overall three patients achieved a complete remission, and one patient had hematologic improvement, for an overall response rate of 28%. Of the responde ...[more]

PMID: 18398735

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Project description:BackgroundHypomethylating agents (HMA), azacitidine, and decitabine are frequently used in the management of myelodysplastic syndromes (MDS). However, there are no clinical trials that have directly compared these agents. We conducted a systematic review and indirectly compared the efficacy of azacitidine to decitabine in MDS.MethodsWe conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus) through June 28, 2018, without language or time restrictions. Studies were screened by two independent reviewers, and differences were resolved by consensus. The fixed effect model and adjusted indirect comparison methods were used to pool relative risks (RR) of major outcomes of interest (mortality, response rate, quality of life, hematologic improvement, hospitalization, leukemia transformation, transfusion independence).ResultsOnly four trials met the eligibility criteria. Two trials compared azacitidine to the best supportive care (BSC) and included 549 patients, and the other two compared decitabine to BSC and included 403 patients. The risk of bias was unclear overall. Compared to BSC, azacitidine was significantly associated with lower mortality (RR = 0.83, 95% CI 0.74-0.94, I2 = 89%) whereas decitabine did not significantly reduce mortality (RR = 0.88, 95% CI 0.77-1.00, I2 = 53%). Both drugs were associated with higher partial and complete response compared to BSC. Indirect comparisons were not statistically significant for all the studied outcomes, except for complete response where azacitidine was less likely to induce complete response compared to decitabine (RR = 0.11, 95% CI = 0.01-0.86, very low-certainty evidence).ConclusionsAzacitidine and decitabine are both associated with improved outcomes compared to BSC. The available indirect evidence comparing the two agents warrants very low certainty and cannot reliably confirm the superiority of either agent. Head-to-head trials are needed. In the meantime, the choice of agent should be driven by patient preferences, adverse effects, drug availability, and cost.

Project description:Background: The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) have been widely used in patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). However, few direct clinical trials have been carried out to compare the efficacy and adverse events (AEs) between these two agents. The clinical choice between them is controversial. A systematic review and network meta-analysis (NMA) was performed to compare the efficacy, safety, and survival of DAC and AZA in AML and HR-MDS patients. Methods: We systematically searched MEDLINE, Embase, Web of Science, and Cochrane Library through March 15, 2021. Randomized controlled trials (RCTs) on AML or HR-MDS patients comparing the efficacy and safety between DAC and AZA or comparing one of HMAs to conventional care regimens (CCR) were selected. Results: Eight RCTs (n = 2,184) were identified in the NMA. Four trials compared AZA to CCR, and four compared DAC to CCR. Direct comparisons indicated that, compared to CCR, both AZA and DAC were associated with higher overall response (OR) rate (AZA vs. CCR: relative risk (RR) = 1.48, 95% CI 1.05-2.1; DAC vs. CCR: RR = 2.14, 95% CI 1.21-3.79) and longer overall survival (OS) (AZA vs. CCR: HR = 0.64, 95% CI 0.50-0.82; DAC vs. CCR: HR = 0.84, 95% CI 0.72-0.98), and AZA showed higher rate of complete remission with incomplete blood count recovery (CRi) (HR = 2.52, 95% CI 1.27-5). For the indirect method, DAC showed a higher complete remission (CR) rate than AZA in patients with both AML (RR = 2.28, 95% CI 1.12-4.65) and MDS (RR = 7.57, 95% CI 1.26-45.54). Additionally, DAC significantly increased the risk of 3/4 grade anemia (RR = 1.61, 95% CI: 1.03-2.51), febrile neutropenia (RR = 4.03, 95% CI: 1.41-11.52), and leukopenia (RR = 3.43, 95% CI 1.64-7.16) compared with AZA. No statistical significance was found for the other studied outcomes. Conclusion: Compared to CCR, both AZA and DAC can promote outcomes in patients with AML and HR-MDS. DAC showed higher efficacy especially CR rate than AZA (low-certainty evidence), while AZA experienced lower frequent grade 3/4 cytopenia than patients receiving DAC treatment.

Dataset Information

Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitidine.

Publications

Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitidine.

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