PMID- 23978644
OWN - NLM
STAT- MEDLINE
DCOM- 20140919
LR  - 20220330
IS  - 2212-5353 (Electronic)
IS  - 2212-5345 (Linking)
VI  - 51
IP  - 3
DP  - 2013 Sep
TI  - Efficacy and safety of low-dose sirolimus for treatment of 
      lymphangioleiomyomatosis.
PG  - 175-83
LID - S2212-5345(13)00040-3 [pii]
LID - 10.1016/j.resinv.2013.03.002 [doi]
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease caused by 
      dysregulated activation of the mammalian target of rapamycin (mTOR). Sirolimus, 
      an inhibitor of mTOR, has been reported to decrease the size of angiomyolipomas 
      and stabilize pulmonary function in patients with LAM. However, the optimal dose 
      for the treatment of LAM remains unclear. METHODS: We conducted a retrospective, 
      observational study of 15 patients with LAM who underwent sirolimus therapy for 
      more than 6 months. The efficacy was evaluated by reviewing the patients' 
      clinical courses, pulmonary function and chest radiologic findings before and 
      after the initiation of sirolimus treatment. RESULTS: All patients had blood 
      trough levels of sirolimus lower than 5ng/mL. Sirolimus treatment improved the 
      annual rates of change in FVC and FEV1 in the 9 patients who were free from 
      chylous effusion (FVC, -101.0 vs. +190.0mL/y, p=0.046 and FEV1, -115.4 vs. 
      +127.8mL/y, p=0.015). The remaining 7 patients had chylous effusion at the start 
      of sirolimus treatment; the chylothorax resolved completely within 1-5 months of 
      treatment in 6 of these cases. These results resembled those of previous studies 
      in which blood trough levels of sirolimus ranged from 5 to 15ng/mL. CONCLUSIONS: 
      Low-dose sirolimus (trough level, 5ng/mL or less) performed as well as the higher 
      doses used previously for improving pulmonary function and decreasing chylous 
      effusion in patients with LAM.
CI  - (c) 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights 
      reserved.
FAU - Ando, Katsutoshi
AU  - Ando K
AD  - Division of Respiratory Medicine, Juntendo University Faculty of Medicine and 
      Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. 
      kando@juntendo.ac.jp
FAU - Kurihara, Masatoshi
AU  - Kurihara M
FAU - Kataoka, Hideyuki
AU  - Kataoka H
FAU - Ueyama, Masako
AU  - Ueyama M
FAU - Togo, Shinsaku
AU  - Togo S
FAU - Sato, Teruhiko
AU  - Sato T
FAU - Doi, Tokuhide
AU  - Doi T
FAU - Iwakami, Shin-ichiro
AU  - Iwakami S
FAU - Takahashi, Kazuhisa
AU  - Takahashi K
FAU - Seyama, Kuniaki
AU  - Seyama K
FAU - Mikami, Masashi
AU  - Mikami M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130530
PL  - Netherlands
TA  - Respir Investig
JT  - Respiratory investigation
JID - 101581124
RN  - 0 (Antibiotics, Antineoplastic)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Respir Investig. 2014 Jul;52(4):274-6. PMID: 24998376
MH  - Adult
MH  - Antibiotics, Antineoplastic/*administration & dosage
MH  - Chylothorax/drug therapy/etiology
MH  - Female
MH  - Forced Expiratory Volume
MH  - Humans
MH  - Lung Neoplasms/complications/*drug therapy/genetics/physiopathology
MH  - Lymphangiomyoma/complications/*drug therapy/genetics/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Molecular Targeted Therapy
MH  - Pleural Effusion, Malignant/drug therapy/etiology
MH  - Retrospective Studies
MH  - Sirolimus/*administration & dosage/blood
MH  - TOR Serine-Threonine Kinases
MH  - Treatment Outcome
MH  - Vital Capacity
OTO - NOTNLM
OT  - Chylous effusion
OT  - Lymphangioleiomyomatosis
OT  - Sirolimus
OT  - mTOR inhibitor
EDAT- 2013/08/28 06:00
MHDA- 2014/09/23 06:00
CRDT- 2013/08/28 06:00
PHST- 2012/11/30 00:00 [received]
PHST- 2013/02/18 00:00 [revised]
PHST- 2013/03/22 00:00 [accepted]
PHST- 2013/08/28 06:00 [entrez]
PHST- 2013/08/28 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
AID - S2212-5345(13)00040-3 [pii]
AID - 10.1016/j.resinv.2013.03.002 [doi]
PST - ppublish
SO  - Respir Investig. 2013 Sep;51(3):175-83. doi: 10.1016/j.resinv.2013.03.002. Epub 
      2013 May 30.