PMID- 20038218
OWN - NLM
STAT- MEDLINE
DCOM- 20100423
LR  - 20211203
IS  - 1029-2403 (Electronic)
IS  - 1042-8194 (Print)
IS  - 1026-8022 (Linking)
VI  - 51
IP  - 2
DP  - 2010 Feb
TI  - Experience with everolimus (RAD001), an oral mammalian target of rapamycin 
      inhibitor, in patients with systemic mastocytosis.
PG  - 269-74
LID - 10.3109/10428190903486220 [doi]
AB  - KIT D816V mutation has been observed in more than 90% of patients with systemic 
      mastocytosis (SM). This mutation constitutively activates the mammalian target of 
      rapamycin (mTOR) signaling pathway. We tested the efficacy of everolimus 
      (RAD001), a novel oral mTOR inhibitor, at a dose of 10 mg daily in an open label, 
      non-comparative Phase II trial for patients with SM. Ten patients were enrolled 
      from April 2007 to October 2008. Median age was 55 years, four were males, seven 
      had indolent and three aggressive SM, and six were previously treated with other 
      agents. Median duration of therapy was 4 months (range 0.2-18). No objective 
      responses were noted. Four patients had a short-lasting subjective improvement in 
      symptoms for a median duration of 3 months (range 3-15). Grade 1-3 diarrhea, 
      mucositis, and neutropenia were the most common adverse effects. No Grade 4 
      toxicity was noted. In conclusion, everolimus does not result in appreciable 
      clinical activity in patients with SM.
FAU - Parikh, Sameer A
AU  - Parikh SA
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, TX 77030, USA.
FAU - Kantarjian, Hagop M
AU  - Kantarjian HM
FAU - Richie, Mary Ann
AU  - Richie MA
FAU - Cortes, Jorge E
AU  - Cortes JE
FAU - Verstovsek, Srdan
AU  - Verstovsek S
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Diarrhea/chemically induced
MH  - Everolimus
MH  - Fatigue/chemically induced
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/adverse effects/therapeutic use
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors
MH  - Male
MH  - Mastocytosis, Systemic/*drug therapy/genetics
MH  - Middle Aged
MH  - Mucositis/chemically induced
MH  - Mutation
MH  - Neutropenia/chemically induced
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Proto-Oncogene Proteins c-kit/genetics
MH  - Sirolimus/adverse effects/*analogs & derivatives/therapeutic use
MH  - TOR Serine-Threonine Kinases
MH  - Treatment Outcome
PMC - PMC4184061
MID - NIHMS629569
COIS- Declaration of interest: The authors report no conflicts of interest. The authors 
      alone are responsible for the content and writing of the article.
EDAT- 2009/12/30 06:00
MHDA- 2010/04/24 06:00
PMCR- 2014/10/03
CRDT- 2009/12/30 06:00
PHST- 2009/12/30 06:00 [entrez]
PHST- 2009/12/30 06:00 [pubmed]
PHST- 2010/04/24 06:00 [medline]
PHST- 2014/10/03 00:00 [pmc-release]
AID - 10.3109/10428190903486220 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2010 Feb;51(2):269-74. doi: 10.3109/10428190903486220.