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: Katsutoshi Ando, Masatoshi Kurihara, Hideyuki Kataoka, Masako Ueyama, Shinsaku Togo, Teruhiko Sato, Tokuhide Doi, Shin-ichiro Iwakami, Kazuhisa Takahashi, Kuniaki Seyama, Masashi Mikami
• Journal: Respiratory investigation (Respir Investig) Vol. 51 Issue 3 Pg. 175-83 (Sep 2013) ISSN: 2212-5353 [Electronic] Netherlands
• PMID: 23978644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• MTOR protein, human
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Adult
• Antibiotics, Antineoplastic (administration & dosage)
• Chylothorax (drug therapy, etiology)
• Female
• Forced Expiratory Volume
• Humans
• Lung Neoplasms (complications, drug therapy, genetics, physiopathology)
• Lymphangiomyoma (complications, drug therapy, genetics, physiopathology)
• Male
• Middle Aged
• Molecular Targeted Therapy
• Pleural Effusion, Malignant (drug therapy, etiology)
• Retrospective Studies
• Sirolimus (administration & dosage, blood)
• TOR Serine-Threonine Kinases
• Treatment Outcome
• Vital Capacity