The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study

Miller, Kenneth B.; Kyungmann, K.; Morrison, Francis S.; Winter, Jane N.; Bennett, John M.; Neiman, Richard S.; Head, David R.; Cassileth, Peter A.; O'Connell, M. J.

doi:10.1007/bf01697631

Cited by 42 publications

(19 citation statements)

References 20 publications

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“…In controlled trials, LDAC has not shown a survival advantage compared with BSC in MDS [17,18], although a recent study by Burnett et al showed an OS benefit in LDAC-treated older patients (median age 74 years) with AML and higher-risk MDS who achieved CR, compared with hydroxyurea [8]. In the Burnett study, survival with LDAC was strongly associated with response: median OS was 80 weeks in patients receiving LDAC who achieved CR vs 18 weeks in patients who did not achieve CR.…”

Section: Discussionmentioning

confidence: 99%

Effects of azacitidine compared with conventional care regimens in elderly (≥75 years) patients with higher-risk myelodysplastic syndromes

Seymour

Fenaux

Silverman

et al. 2010

Critical Reviews in Oncology/Hematology

107

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This analysis compared azacitidine (AZA) to conventional care regimens (CCR) and their associated overall survival (OS) and tolerability in the subset of 87 elderly (≥75 years) patients with higher-risk MDS (FAB: RAEB, RAEB-t, CMML and IPSS: Int-2 or High) from the AZA-001 trial. Patients were randomized to AZA (75 mg/m2/day subcutaneously×7 days every 28 days) (n = 38) or CCR (n = 49) and had median ages of 78 and 77 years, respectively. AZA significantly improved OS vs CCR (HR: 0.48 [95%CI: 0.26, 0.89]; p = 0.0193) and 2-year OS rates were 55% vs 15% (p < 0.001), respectively. AZA was generally well tolerated compared with CCR, which was primarily best supportive care (67%). Grade 3–4 anemia, neutropenia, and thrombocytopenia with AZA vs CCR were 13% vs 4%, 61% vs 17%, and 50% vs 30%, respectively. Given this efficacy and tolerability, AZA should be considered the treatment of choice in patients aged ≥75 years with good performance status and higher-risk MDS.

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Section: Discussionmentioning

confidence: 99%

Effects of azacitidine compared with conventional care regimens in elderly (≥75 years) patients with higher-risk myelodysplastic syndromes

Seymour

Fenaux

Silverman

et al. 2010

Critical Reviews in Oncology/Hematology

107

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“…Low‐ and high‐dose chemotherapy. Low‐dose chemo is generally not considered to be indicated in low‐risk MDS because of toxicity or limited efficacy [198]. AML‐like intensive chemotherapy should only be considered in high‐risk MDS, although no survival benefit has been demonstrated unless CR is followed by allo‐SCT [199].…”

mentioning

confidence: 99%

Myelodysplastic syndromes: biology and treatment

Jädersten

Hellström‐Lindberg

2009

Journal of Internal Medicine

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Optimal management of patients with myelodysplastic syndromes (MDS) requires an insight into the biology of the disease and the mechanisms of action of the available therapies. This review focuses on low-risk MDS, for which chronic anaemia and eventual progression to acute myeloid leukaemia are the main concerns. We cover the updated World Health Organization classification, the latest prognostic scoring system, and describe novel findings in the pathogenesis of 5q) syndrome. We perform in depth analyses of two of the most widely used treatments, erythropoietin and lenalidomide, discussing mechanisms of action, reasons for treatment failure and influence on survival.

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“…Low dose cytosine arabinoside alone has been extensively used in higher-risk MDS, where it yields CR, PR and HI in 10-15%, 15-20% and 15-20% of patients, respectively, with a median survival of 13-16 months (Miller et al, 1992;Zwierzina et al, 2005;Fenaux et al, 2010). However, it is unclear whether LDAC alone can improve survival over best supportive care in higher-risk MDS.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib combined with low‐dose cytarabine in Intermediate‐2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM

et al. 2012

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Summary Marrow cells from patients with higher‐risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)‐κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher‐risk MDS patients with bortezomib (1·5 mg/m2, days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m2, then 20 mg/m2 from days 1–14), every 28 d for four cycles. Median follow‐up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n = 1), marrow‐CR (n = 3), partial response (PR, n = 5) and haematological improvement (HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients (P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow‐CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1–2 pre‐treatment haematotoxicity developed Grade 3–4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher‐risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes.

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The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study

Cited by 42 publications

References 20 publications

Effects of azacitidine compared with conventional care regimens in elderly (≥75 years) patients with higher-risk myelodysplastic syndromes

Effects of azacitidine compared with conventional care regimens in elderly (≥75 years) patients with higher-risk myelodysplastic syndromes

Myelodysplastic syndromes: biology and treatment

Bortezomib combined with low‐dose cytarabine in Intermediate‐2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM

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