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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 reduction in bilateral renal angiomyolipoma volume.
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f02: Abdominal CT scans taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing a reduction in bilateral renal angiomyolipoma volume.

Mentions: A 25-year-old patient diagnosed with LAM and TSC presented with a two-year history of recurrent pneumothorax and pleurodesis. She reported no smoking and had no relevant exposure history. Because of the neurological impairment associated with TSC, the patient had frequent convulsive seizures and a cognitive deficit. She also had large bilateral renal angiomyolipomas and had previously undergone a right partial nephrectomy because of hemorrhage. She had been using goserelin and doxycycline since 2010, and the renal tumor had progressively increased in the last two years. A decision was made to treat her with sirolimus, initially at 6 mg/day and subsequently at 2 mg/day because of nausea and vomiting. After 12 months of treatment, there was a significant reduction in the size of the angiomyolipoma (from approximately 20 cm, with confluent masses, to approximately 3 cm; Figure 2). Because of her cognitive deficit, the patient did not undergo pulmonary function testing.


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 reduction in bilateral renal angiomyolipoma volume.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f02: Abdominal CT scans taken before treatment with sirolimus (in A) and after 12 months of treatment with the drug (in B), showing a reduction in bilateral renal angiomyolipoma volume.
Mentions: A 25-year-old patient diagnosed with LAM and TSC presented with a two-year history of recurrent pneumothorax and pleurodesis. She reported no smoking and had no relevant exposure history. Because of the neurological impairment associated with TSC, the patient had frequent convulsive seizures and a cognitive deficit. She also had large bilateral renal angiomyolipomas and had previously undergone a right partial nephrectomy because of hemorrhage. She had been using goserelin and doxycycline since 2010, and the renal tumor had progressively increased in the last two years. A decision was made to treat her with sirolimus, initially at 6 mg/day and subsequently at 2 mg/day because of nausea and vomiting. After 12 months of treatment, there was a significant reduction in the size of the angiomyolipoma (from approximately 20 cm, with confluent masses, to approximately 3 cm; Figure 2). Because of her cognitive deficit, the patient did not undergo pulmonary function testing.

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