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Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations.

Freitas CS, Baldi BG, Araújo MS, Heiden GI, Kairalla RA, Carvalho CR - J Bras Pneumol (2015 May-Jun)

Bottom Line: The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement.However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

View Article: PubMed Central - PubMed

Affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.

ABSTRACT

Objective: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).

Methods: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus.

Results: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma.

Conclusions: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

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Related in: MedlinePlus

Abdominal CT scans taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing a significant reduction in retroperitoneal lymphangioleiomyoma volume (white arrow).
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f03: Abdominal CT scans taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing a significant reduction in retroperitoneal lymphangioleiomyoma volume (white arrow).

Mentions: A 26-year-old nonsmoker with a three-year history of dyspnea on exertion presented with acute worsening of dyspnea. Although a large chylothorax was identified in 2011, it was not investigated at the time. One year later, the patient was admitted for investigation. Chest and abdominal CT scans showed diffuse cysts in the lung parenchyma, as well as large retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. A diagnosis of LAM was established, and initial pulmonary function test results were as follows: FVC, 2.36 L (61% of predicted); FEV1, 1.49 L (46% of predicted); and FEV1/FVC, 0.63. The patient was started on sirolimus (at 2 mg/day) and after 12 months of treatment with the drug showed significant regression of the retroperitoneal and abdominal masses (Figure 3), as well as improved lung function (Table 1).


Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations.

Freitas CS, Baldi BG, Araújo MS, Heiden GI, Kairalla RA, Carvalho CR - J Bras Pneumol (2015 May-Jun)

Abdominal CT scans taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing a significant reduction in retroperitoneal lymphangioleiomyoma volume (white arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4541764&req=5

f03: Abdominal CT scans taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing a significant reduction in retroperitoneal lymphangioleiomyoma volume (white arrow).
Mentions: A 26-year-old nonsmoker with a three-year history of dyspnea on exertion presented with acute worsening of dyspnea. Although a large chylothorax was identified in 2011, it was not investigated at the time. One year later, the patient was admitted for investigation. Chest and abdominal CT scans showed diffuse cysts in the lung parenchyma, as well as large retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. A diagnosis of LAM was established, and initial pulmonary function test results were as follows: FVC, 2.36 L (61% of predicted); FEV1, 1.49 L (46% of predicted); and FEV1/FVC, 0.63. The patient was started on sirolimus (at 2 mg/day) and after 12 months of treatment with the drug showed significant regression of the retroperitoneal and abdominal masses (Figure 3), as well as improved lung function (Table 1).

Bottom Line: The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement.However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

View Article: PubMed Central - PubMed

Affiliation: Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.

ABSTRACT

Objective: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day).

Methods: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus.

Results: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma.

Conclusions: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

Show MeSH
Related in: MedlinePlus