PMID- 27795561
OWN - NLM
STAT- MEDLINE
DCOM- 20170901
LR  - 20181113
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 31
IP  - 2
DP  - 2017 Feb
TI  - A clinical trial for patients with acute myeloid leukemia or myelodysplastic 
      syndromes not eligible for standard clinical trials.
PG  - 318-324
LID - 10.1038/leu.2016.303 [doi]
AB  - Most clinical trials exclude patients with poor performance or comorbidities. To 
      study whether patients with these characteristics can be treated within a 
      clinical trial, we conducted a study for patients with acute myeloid leukemia 
      (AML) or myelodysplastic syndromes (MDS) with poor performance, organ dysfunction 
      or comorbidities. Primary endpoint was 60-day survival. Study included stopping 
      rules for survival and response. Treatment consisted on a combination of 
      azacitidine and vorinostat. Thirty patients (16 with MDS, 14 with AML) were 
      enrolled. Median follow-up was 7.4 months (0.3-29). Sixty-day survival was 83%. 
      No stopping rules were met. Main adverse events (AEs) were grades 1 and 2 
      gastrointestinal toxicities. In view of these results, we expanded the study and 
      treated 79 additional patients: 27 with azacitidine (AZA) and 52 with azacitidine 
      and vorinostat (AZA+V). Median follow-up was 22.7 months (12.6-47.5). Sixty-day 
      survival rate was 79% (AZA=67%, AZA+V=85%, P=0.07). Median overall survival was 
      7.6 months (4.5-10.7). Median event-free survival was 4.5 months (3.5-5.6). Main 
      AEs included grades 1 and 2 gastrointestinal toxicities. Our results suggest this 
      subset of patients can be safely treated within clinical trials and derive 
      clinical benefit. Relaxation of standard exclusion criteria may increase the pool 
      of patients likely to benefit from therapy.
FAU - Montalban-Bravo, G
AU  - Montalban-Bravo G
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Huang, X
AU  - Huang X
AD  - Department of Biostatistics, University of Texas, MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Naqvi, K
AU  - Naqvi K
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Jabbour, E
AU  - Jabbour E
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Borthakur, G
AU  - Borthakur G
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - DiNardo, C D
AU  - DiNardo CD
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Pemmaraju, N
AU  - Pemmaraju N
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Cortes, J
AU  - Cortes J
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Verstovsek, S
AU  - Verstovsek S
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Kadia, T
AU  - Kadia T
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Daver, N
AU  - Daver N
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Wierda, W
AU  - Wierda W
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Alvarado, Y
AU  - Alvarado Y
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Konopleva, M
AU  - Konopleva M
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Ravandi, F
AU  - Ravandi F
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Estrov, Z
AU  - Estrov Z
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Jain, N
AU  - Jain N
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Alfonso, A
AU  - Alfonso A
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Brandt, M
AU  - Brandt M
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Sneed, T
AU  - Sneed T
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Chen, H-C
AU  - Chen HC
AD  - Department of Biostatistics, University of Texas, MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Yang, H
AU  - Yang H
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Bueso-Ramos, C
AU  - Bueso-Ramos C
AD  - Department of Hematopathology, University of Texas, MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Pierce, S
AU  - Pierce S
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Estey, E
AU  - Estey E
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Bohannan, Z
AU  - Bohannan Z
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Kantarjian, H M
AU  - Kantarjian HM
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
FAU - Garcia-Manero, G
AU  - Garcia-Manero G
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00948064
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161031
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Biomarkers)
SB  - IM
EIN - Leukemia. 2017 Jul;31(7):1659. PMID: 28338082
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Biomarkers
MH  - Bone Marrow/pathology
MH  - Chromosome Aberrations
MH  - Comorbidity
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Leukemia, Myeloid, Acute/*drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/*drug therapy/genetics/mortality
MH  - Treatment Outcome
EDAT- 2016/11/01 06:00
MHDA- 2017/09/02 06:00
CRDT- 2016/11/01 06:00
PHST- 2016/07/04 00:00 [received]
PHST- 2016/08/21 00:00 [revised]
PHST- 2016/08/30 00:00 [accepted]
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2017/09/02 06:00 [medline]
PHST- 2016/11/01 06:00 [entrez]
AID - leu2016303 [pii]
AID - 10.1038/leu.2016.303 [doi]
PST - ppublish
SO  - Leukemia. 2017 Feb;31(2):318-324. doi: 10.1038/leu.2016.303. Epub 2016 Oct 31.