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A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome.
Raza, Azra; Galili, Naomi; Smith, Scott E; Godwin, John; Boccia, Ralph V; Myint, Han; Mahadevan, Daruka; Mulford, Deborah; Rarick, Mark; Brown, Gail L; Schaar, Dale; Faderl, Stefan; Komrokji, Rami S; List, Alan F; Sekeres, Mikkael.
Afiliação
  • Raza A; Columbia University Medical Center, Milstein Hospital Bldg., 6N-435, 177 Fort Washington Avenue, New York, NY 10032, USA. azra.raza@columbia.edu
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glutationa / Antineoplásicos Tipo de estudo: Clinical_trials / Etiology_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glutationa / Antineoplásicos Tipo de estudo: Clinical_trials / Etiology_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos