Effect of azacitidine (AZA) on overall survival in higher-risk myelodysplastic syndromes (MDS) without complete remission

List, Alan F.; Fenaux, Pierre; Mufti, Ghulam J.; Hellström‐Lindberg, Eva; Gore, S; Bennett, John M.; Silverman, L.R.; Backstrom, Jay T.; Allen, Amanda; Beach, C.L.

doi:10.1200/jco.2008.26.15_suppl.7006

Cited by 41 publications

(35 citation statements)

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“…This may be explained by the fact that even disease stabilization confers an overall survival advantage for patients treated with 5-AZA, as shown by the recently presented data of the AZA-001 trial [23]. On the basis of these observations, continuous administration of 5-AZA until progression may not be necessary.…”

Section: Discussionmentioning

confidence: 85%

A limited number of 5-azacitidine cycles can be effective treatment in MDS

et al. 2008

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International audienceHypomethylating agents, such as 5-azacitidine (5-AZA) and 5-aza-2'-deoxycytidine (decitabine), have recently been approved for the treatment of myelodysplastic syndromes (MDS). Several randomized trials have shown favorable results concerning response rate, survival, transformation to acute leukemia, and quality of life. In these trials, treatment was administered continuously until progression. In the retrospective study presented here, we evaluated the outcome of patients with higher risk MDS or secondary acute myeloid leukemia (sAML) treated with a limited number of 5-AZA cycles. A total of 32 patients received 5-AZA alone ( = 30) or in combination with valproic acid and all-trans retinoic acid ( = 2). 5-AZA was administered subcutaneously at a fixed dose of 75 mg/m daily for 7 days and repeated every 28 days. 5-AZA was given for a median of four courses. Treatment was continued for two more cycles as consolidation in patients who had achieved complete remission (CR), marrow CR, or stable disease with hematologic improvement. The overall response rate was 50% according to the modified International Working Group criteria. Complete remissions were achieved in 15.6% and stable disease in 34.4% of patients. Peripheral blood counts normalized in 6.3% of patients while hematologic improvement was achieved in 25%. The median time to AML in responding patients was 45 weeks, while AML occurred after a median of 14 weeks in non-responding patients ( = .038). The median survival of all patients was 60 weeks; the median survival of responders was 74 weeks compared with 26 weeks in non-responders ( = .047). In this retrospective analysis, 5-AZA was associated with a survival advantage in responding patients with higher risk MDS or sAML. These favorable results suggest that patients may benefit even from a limited number of courses of 5-AZA. A randomized controlled clinical trial is required to prospectively validate these findings

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Section: Discussionmentioning

confidence: 85%

A limited number of 5-azacitidine cycles can be effective treatment in MDS

et al. 2008

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“…As further analyses of patient subgroups in the AZA-001 trial have shown, even hematologic improvement as defined by the IWG criteria confers an overall survival advantage for patients treated with azacitidine. 69 In this analysis, one year survival was improved with azacitidine compared to conventional care in all IWG response categories. These results call into question the current paradigm that achievement of complete remission is necessary to prolong survival in MDS.…”

Section: Dosing Of Azacitidine and Duration Of Therapymentioning

confidence: 94%

The role of azacitidine in the management of myelodysplastic syndromes (MDS)

Goetze¹

2009

CMAR

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Myelodysplastic syndromes (MDS) are a group of common bone marrow disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and a propensity for transformation to acute myeloid leukemia (AML). For many years, the main treatment option for MDS was best supportive care which alleviates symptoms but has no effect on the natural course of the disease. The recent approval of the demethylating agent azacitidine represents a significant advance in the treatment of MDS. The results of two randomized trials with azacitidine have shown an overall response rate between 40% and 60%, an improved quality of life, a reduced risk of transformation to AML and a definite survival advantage compared to best supportive care or low-dose chemotherapy. Current data on azacitidine and its place in the treatment of MDS are reviewed.

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“…Another important observation was that complete remission (CR) is not required in order to achieve a survival advantage. Patients who achieved partial remission (PR) and histologic improvement (HI) demonstrated a survival benefit with azacitidine treatment (13). Patients with stable disease had a survival benefit compared with those with progression, but this was seen in those treated with azacitidine or CCR (14).…”

Section: Azanucleosides In the Mdssmentioning

confidence: 99%

Clinical development of demethylating agents in hematology

Navada¹,

Steinmann²,

Lübbert³

et al. 2014

J. Clin. Invest.

133

112

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The term epigenetics refers to the heritable changes in gene expression that are not associated with a change in the actual DNA sequence. Epigenetic dysregulation is linked to the pathogenesis of a number of malignancies and has been studied extensively in myelodysplastic syndromes and acute myeloid leukemia. DNA methylation is frequently altered in cancerous cells and likely results in transcriptional silencing of tumor suppressor genes. Re-expression of these genes by inhibition of the DNA methyltransferases has been successful in the treatment of benign and malignant disease. In this Review, we discuss the clinical development of demethylating agents in hematology, with a focus on azacitidine and decitabine.

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Effect of azacitidine (AZA) on overall survival in higher-risk myelodysplastic syndromes (MDS) without complete remission

Cited by 41 publications

References 0 publications

A limited number of 5-azacitidine cycles can be effective treatment in MDS

A limited number of 5-azacitidine cycles can be effective treatment in MDS

The role of azacitidine in the management of myelodysplastic syndromes (MDS)

Clinical development of demethylating agents in hematology

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