PMID- 18704419
OWN - NLM
STAT- MEDLINE
DCOM- 20090206
LR  - 20211203
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Linking)
VI  - 88
IP  - 3
DP  - 2009 Mar
TI  - A pilot trial of the mTOR (mammalian target of rapamycin) inhibitor RAD001 in 
      patients with advanced B-CLL.
PG  - 221-7
LID - 10.1007/s00277-008-0582-9 [doi]
AB  - Although B-cell chronic lymphocytic leukemia (CLL) is treatable, it remains an 
      incurable disease and most patients inevitably suffer relapse. Many therapeutic 
      options exist for those requiring therapy, including monoclonal antibodies and 
      stem cell transplantation, but remissions tend to last shorter in the course of 
      the disease. Targeting the cell cycle has recently been realized to be an 
      attractive therapeutic approach in solid and hematological malignancies, and the 
      proliferative nature of B-CLL is increasingly accepted. Here, we report data on a 
      phase II pilot trial with the oral mammalian target of rapamycin (mTOR) inhibitor 
      RAD001 5 mg/daily in patients with advanced B-CLL who had progressive disease 
      after at least two lines of treatment. After treatment of seven patients, this 
      trial was stopped because of toxicity concerns, although some degree of activity 
      was observed (one partial remission, three patients with stable disease). 
      Interestingly, cyclin E expression decreased in responding patients. Further 
      strategies of mTOR inhibition by RAD001 in B-CLL should focus on different 
      treatment schedules, adequate anti-infectious prophylaxis, or combinations with 
      cytotoxic drugs.
FAU - Decker, Thomas
AU  - Decker T
AD  - III. Department of Medicine, Technical University of Munich, Ismaningerstr. 15, 
      81675 Munich, Germany. t.decker@lrz.tum.de
FAU - Sandherr, Michael
AU  - Sandherr M
FAU - Goetze, Katharina
AU  - Goetze K
FAU - Oelsner, Madlen
AU  - Oelsner M
FAU - Ringshausen, Ingo
AU  - Ringshausen I
FAU - Peschel, Christian
AU  - Peschel C
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080814
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.- (Protein Kinases)
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  - Cell Cycle/drug effects/physiology
MH  - Everolimus
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/mortality/pathology
MH  - Pilot Projects
MH  - Pneumonia/chemically induced/diagnosis
MH  - Protein Kinases/*physiology
MH  - Sirolimus/adverse effects/*analogs & derivatives/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases
EDAT- 2008/08/16 09:00
MHDA- 2009/02/07 09:00
CRDT- 2008/08/16 09:00
PHST- 2008/02/27 00:00 [received]
PHST- 2008/07/24 00:00 [accepted]
PHST- 2008/08/16 09:00 [pubmed]
PHST- 2009/02/07 09:00 [medline]
PHST- 2008/08/16 09:00 [entrez]
AID - 10.1007/s00277-008-0582-9 [doi]
PST - ppublish
SO  - Ann Hematol. 2009 Mar;88(3):221-7. doi: 10.1007/s00277-008-0582-9. Epub 2008 Aug 
      14.