A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome.
Cancer
; 118(8): 2138-47, 2012 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-21887679
ABSTRACT
BACKGROUND:
Ezatiostat is a glutathione analog prodrug glutathione S-transferase P1-1 (GSTP1-1) inhibitor. This study evaluated 2 extended dose schedules of oral ezatiostat in 89 heavily pretreated patients with low to intermediate-1 risk myelodysplastic syndrome (MDS).METHODS:
Patients were randomized by 1 stratification factor-baseline cytopenia (anemia only vs anemia with additional cytopenias)-to 1 of 2 extended dosing schedules. Multilineage hematologic improvement (HI) responses were assessed by International Working Group 2006 criteria.RESULTS:
Overall, 11 of 38 (29%) red blood cell (RBC) transfusion-dependent patients had HI-Erythroid (HI-E) response. The median duration of HI-E response was 34 weeks. Multilineage responses were observed. There was 1 cytogenetic complete response in a del (5q) MDS patient. An important trend was the effect of prior therapy on response. A 40% HI-E rate (6 of 15 patients) was observed in patients who had prior lenalidomide and no prior hypomethylating agents (HMAs), with 5 of 11 (45%) patients achieving significant RBC transfusion reduction and 3 of 11 (27%) achieving transfusion independence. A 28% HI-E rate (5 of 18 patients) was observed in patients who were both lenalidomide and HMA naive, with 4 of 8 (50%) patients achieving clinically significant RBC transfusion reductions. Most common ezatiostat-related adverse events were grade 1 and 2 gastrointestinal including nausea (45%, 17%), diarrhea (26%, 7%), and vomiting (30%, 12%).CONCLUSIONS:
Ezatiostat is the first GSTP1-1 inhibitor shown to cause clinically significant and sustained reduction in RBC transfusions, transfusion independence, and multilineage responses in MDS patients. The tolerability and activity profile of ezatiostat may offer a new treatment option for patients with MDS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glutationa
/
Antineoplásicos
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos