PMID- 24851266
OWN - NLM
STAT- MEDLINE
DCOM- 20140604
LR  - 20220311
IS  - 1545-5017 (Electronic)
IS  - 1545-5009 (Linking)
VI  - 61
IP  - 6
DP  - 2014 Jun
TI  - Sirolimus for non-progressive NF1-associated plexiform neurofibromas: an NF 
      clinical trials consortium phase II study.
PG  - 982-6
AB  - BACKGROUND: Patients with Neurofibromatosis Type 1 (NF1) have an increased risk 
      of developing tumors of the central and peripheral nervous system, including 
      plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among 
      the most debilitating complications of NF1. There are no standard treatment 
      options for PN other than surgery, which is often difficult due to the extensive 
      growth and invasion of surrounding tissues. Mammalian Target of Rapamycin (mTOR) 
      acts as a master switch of cellular catabolism and anabolism and controls protein 
      translation, angiogenesis, cell motility, and proliferation. The NF1 tumor 
      suppressor, neurofibromin, regulates the mTOR pathway activity. Sirolimus is a 
      macrolide antibiotic that inhibits mTOR activity. PROCEDURE: We conducted a 
      2-stratum phase II clinical trial. In stratum 2, we sought to determine whether 
      the mTOR inhibitor sirolimus in subjects with NF1 results in objective 
      radiographic responses in inoperable PNs in the absence of documented 
      radiographic progression at trial entry. RESULTS: No subjects had better than 
      stable disease by the end of six courses. However, the children's self-report 
      responses on health-related quality of life questionnaires indicated a 
      significant improvement in the mean scores of the Emotional and School domains 
      from baseline to 6 months of sirolimus. CONCLUSIONS: This study efficiently 
      documented that sirolimus does not cause shrinkage of non-progressive PNs, and 
      thus should not be considered as a treatment option for these tumors. This study 
      also supports the inclusion of patient-reported outcome measures in clinical 
      trials to assess areas of benefit that are not addressed by the medical outcomes.
CI  - (c) 2013 Wiley Periodicals, Inc.
FAU - Weiss, Brian
AU  - Weiss B
FAU - Widemann, Brigitte C
AU  - Widemann BC
FAU - Wolters, Pamela
AU  - Wolters P
FAU - Dombi, Eva
AU  - Dombi E
FAU - Vinks, Alexander A
AU  - Vinks AA
FAU - Cantor, Alan
AU  - Cantor A
FAU - Korf, Bruce
AU  - Korf B
FAU - Perentesis, John
AU  - Perentesis J
FAU - Gutmann, David H
AU  - Gutmann DH
FAU - Schorry, Elizabeth
AU  - Schorry E
FAU - Packer, Roger
AU  - Packer R
FAU - Fisher, Michael J
AU  - Fisher MJ
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
RN  - 0 (Protein Kinase Inhibitors)
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  - Adolescent
MH  - Child
MH  - Child, Preschool
MH  - Diarrhea/chemically induced
MH  - Emotions
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Neurofibroma, Plexiform/*drug therapy/etiology/pathology/psychology
MH  - Neurofibromatosis 1/*drug therapy/psychology
MH  - Pain Measurement
MH  - Protein Kinase Inhibitors/adverse effects/*therapeutic use
MH  - Quality of Life
MH  - Sirolimus/adverse effects/*therapeutic use
MH  - Soft Tissue Neoplasms/*drug therapy/etiology/pathology
MH  - Surveys and Questionnaires
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/physiology
MH  - Treatment Outcome
MH  - Tumor Burden/drug effects
EDAT- 2014/05/23 06:00
MHDA- 2014/06/05 06:00
CRDT- 2014/05/23 06:00
PHST- 2014/05/23 06:00 [entrez]
PHST- 2014/05/23 06:00 [pubmed]
PHST- 2014/06/05 06:00 [medline]
AID - 10.1002/pbc.24873 [doi]
PST - ppublish
SO  - Pediatr Blood Cancer. 2014 Jun;61(6):982-6. doi: 10.1002/pbc.24873.