PMID- 22082314
OWN - NLM
STAT- MEDLINE
DCOM- 20120502
LR  - 20231120
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Linking)
VI  - 156
IP  - 2
DP  - 2012 Jan
TI  - Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as 
      salvage therapy for older patients with acute myeloid leukaemia: results of a 
      phase II GIMEMA study (AML-1107).
PG  - 205-12
LID - 10.1111/j.1365-2141.2011.08940.x [doi]
AB  - The mammalian target of rapamycin (mTOR) signalling pathway has emerged as an 
      important therapeutic target for acute myeloid leukaemia (AML). This study 
      assessed the combination of temsirolimus, an mTOR inhibitor, and lower-dose 
      clofarabine as salvage therapy in older patients with AML. Induction consisted of 
      clofarabine 20mg/m(2) on days 1-5 and temsirolimus 25mg (flat dose) on days 1, 8 
      and 15. Patients achieving complete remission with (CR) or without (CRi) full 
      haematological recovery could receive monthly temsirolimus maintenance. In 53 
      evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). 
      Median disease-free survival was 3.5months, and median overall survival was 
      4months (9.1months for responders). The most common non-haematological severe 
      adverse events included infection (48%), febrile neutropenia (34%) and 
      transaminitis (11%). The 30-d all-cause induction mortality was 13%. Laboratory 
      data from 25 patients demonstrated that a >50%in vivo inhibition of S6 ribosomal 
      protein phosphorylation was highly correlated with response rate (75% with 
      inhibition versus 0% without inhibition; P=0.0001), suggesting that targeting the 
      mTOR pathway is clinically relevant. The acceptable safety profile and the 
      predictive value of target inhibition encourage further investigation of this 
      novel regimen.
CI  - (c) 2011 Blackwell Publishing Ltd.
FAU - Amadori, Sergio
AU  - Amadori S
AD  - Department of Haematology, Tor Vergata University Hospital, Roma, Italy 
      Department of Haematology, St. George's Hospital, London, UK. 
      sergio.amadori@ptvonline.it
FAU - Stasi, Roberto
AU  - Stasi R
FAU - Martelli, Alberto M
AU  - Martelli AM
FAU - Venditti, Adriano
AU  - Venditti A
FAU - Meloni, Giovanna
AU  - Meloni G
FAU - Pane, Fabrizio
AU  - Pane F
FAU - Martinelli, Giovanni
AU  - Martinelli G
FAU - Lunghi, Monia
AU  - Lunghi M
FAU - Pagano, Livio
AU  - Pagano L
FAU - Cilloni, Daniela
AU  - Cilloni D
FAU - Rossetti, Elena
AU  - Rossetti E
FAU - Di Raimondo, Francesco
AU  - Di Raimondo F
FAU - Fozza, Claudio
AU  - Fozza C
FAU - Annino, Luciana
AU  - Annino L
FAU - Chiarini, Francesca
AU  - Chiarini F
FAU - Ricci, Francesca
AU  - Ricci F
FAU - Ammatuna, Emanuele
AU  - Ammatuna E
FAU - La Sala, Edoardo
AU  - La Sala E
FAU - Fazi, Paola
AU  - Fazi P
FAU - Vignetti, Marco
AU  - Vignetti M
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20111115
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Adenine Nucleotides)
RN  - 0 (Arabinonucleosides)
RN  - 624KN6GM2T (temsirolimus)
RN  - 762RDY0Y2H (Clofarabine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenine Nucleotides/administration & dosage/adverse effects
MH  - Age Factors
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Arabinonucleosides/administration & dosage/adverse effects
MH  - Clofarabine
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Salvage Therapy/*methods
MH  - Sirolimus/administration & dosage/adverse effects/analogs & derivatives
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
EDAT- 2011/11/16 06:00
MHDA- 2012/05/04 06:00
CRDT- 2011/11/16 06:00
PHST- 2011/11/16 06:00 [entrez]
PHST- 2011/11/16 06:00 [pubmed]
PHST- 2012/05/04 06:00 [medline]
AID - 10.1111/j.1365-2141.2011.08940.x [doi]
PST - ppublish
SO  - Br J Haematol. 2012 Jan;156(2):205-12. doi: 10.1111/j.1365-2141.2011.08940.x. 
      Epub 2011 Nov 15.