PMID- 22546242
OWN - NLM
STAT- MEDLINE
DCOM- 20121220
LR  - 20211021
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 5
DP  - 2012 Apr 30
TI  - Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with 
      lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk 
      myelodysplastic syndrome (MDS).
PG  - 18
LID - 10.1186/1756-8722-5-18 [doi]
AB  - BACKGROUND: Ezatiostat, a glutathione S-transferase P1-1 inhibitor, promotes the 
      maturation of hematopoietic progenitors and induces apoptosis in cancer cells. 
      RESULTS: Ezatiostat was administered to 19 patients with non-deletion(5q) 
      myelodysplastic syndrome (MDS) at one of two doses (2000 mg or 2500 mg/day) in 
      combination with 10 mg of lenalidomide on days 1-21 of a 28-day cycle. No 
      unexpected toxicities occurred and the incidence and severity of adverse events 
      (AEs) were consistent with that expected for each drug alone. The most common 
      non-hematologic AEs related to ezatiostat in combination with lenalidomide were 
      mostly grade 1 and 2 fatigue, anorexia, nausea, diarrhea, and vomiting; 
      hematologic AEs due to lenalidomide were thrombocytopenia, neutropenia, and 
      anemia. One of 4 evaluable patients (25%) in the 2500/10 mg dose group 
      experienced an erythroid hematologic improvement (HI-E) response by 2006 MDS 
      International Working Group (IWG) criteria. Four of 10 evaluable patients (40%) 
      in the 2000 mg/10 mg dose group experienced an HI-E response. Three of 7 (43%) 
      red blood cell (RBC) transfusion-dependent patients became RBC transfusion 
      independent, including one patient for whom prior lenalidomide monotherapy was 
      ineffective. Three of 5 (60%) thrombocytopenic patients had an HI-platelet (HI-P) 
      response. Bilineage HI-E and HI-P responses occurred in 3 of 5 (60%), 1 of 3 with 
      HI-E and HI-N (33%), and 1 of 3 with HI-N and HI-P (33%). One of 3 patients (33%) 
      with pancytopenia experienced a complete trilineage response. All multilineage 
      responses were observed in the 2000/10 mg doses recommended for future studies. 
      CONCLUSIONS: The tolerability and activity profile of ezatiostat co-administered 
      with lenalidomide supports the further development of ezatiostat in combination 
      with lenalidomide in MDS and also encourages studies of this combination in other 
      hematologic malignancies where lenalidomide is active.
FAU - Raza, Azra
AU  - Raza A
AD  - Columbia University Medical Center, New York, NY, USA. azra.raza@columbia.edu
FAU - Galili, Naomi
AU  - Galili N
FAU - Mulford, Deborah
AU  - Mulford D
FAU - Smith, Scott E
AU  - Smith SE
FAU - Brown, Gail L
AU  - Brown GL
FAU - Steensma, David P
AU  - Steensma DP
FAU - Lyons, Roger M
AU  - Lyons RM
FAU - Boccia, Ralph
AU  - Boccia R
FAU - Sekeres, Mikkael A
AU  - Sekeres MA
FAU - Garcia-Manero, Guillermo
AU  - Garcia-Manero G
FAU - Mesa, Ruben A
AU  - Mesa RA
LA  - eng
SI  - ClinicalTrials.gov/NCT01062152
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120430
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (Antineoplastic Agents)
RN  - 0 (gamma-Glu-S-BzCys-PhGly diethyl ester)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - F0P408N6V4 (Lenalidomide)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 5/*genetics
MH  - Drug Therapy, Combination
MH  - Female
MH  - Glutathione/*analogs & derivatives/therapeutic use
MH  - Glutathione Transferase/antagonists & inhibitors/metabolism
MH  - Humans
MH  - Lenalidomide
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/*drug therapy/genetics
MH  - Prognosis
MH  - Thalidomide/*analogs & derivatives/therapeutic use
PMC - PMC3416694
EDAT- 2012/05/02 06:00
MHDA- 2012/12/21 06:00
PMCR- 2012/04/30
CRDT- 2012/05/02 06:00
PHST- 2012/01/31 00:00 [received]
PHST- 2012/04/03 00:00 [accepted]
PHST- 2012/05/02 06:00 [entrez]
PHST- 2012/05/02 06:00 [pubmed]
PHST- 2012/12/21 06:00 [medline]
PHST- 2012/04/30 00:00 [pmc-release]
AID - 1756-8722-5-18 [pii]
AID - 10.1186/1756-8722-5-18 [doi]
PST - epublish
SO  - J Hematol Oncol. 2012 Apr 30;5:18. doi: 10.1186/1756-8722-5-18.