title: Efficacy and safety of low-dose sirolimus for treatment of lymphangioleiomyomatosis.
abstract: 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.
authors: 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
authors: Katsutoshi
authors: K
authors: Ando
authors: Masatoshi
authors: M
authors: Kurihara
authors: Hideyuki
authors: H
authors: Kataoka
authors: Masako
authors: M
authors: Ueyama
authors: Shinsaku
authors: S
authors: Togo
authors: Teruhiko
authors: T
authors: Sato
authors: Tokuhide
authors: T
authors: Doi
authors: Shin-ichiro
authors: S
authors: Iwakami
authors: Kazuhisa
authors: K
authors: Takahashi
authors: Kuniaki
authors: K
authors: Seyama
authors: Masashi
authors: M
authors: Mikami
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D002916:Chylothorax / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008203:Lymphangiomyoma / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D016066:Pleural Effusion, Malignant / Q000188:drug therapy / Q000209:etiology; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage* / Q000097:blood; D058570:TOR Serine-Threonine Kinases; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D000903:Antibiotics, Antineoplastic; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Chylous effusion; Lymphangioleiomyomatosis; Sirolimus; mTOR inhibitor