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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

TC de abdome antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando diminuição do volume dos angiomiolipomas renais bilaterais.
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f06: TC de abdome antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando diminuição do volume dos angiomiolipomas renais bilaterais.

Mentions: Uma paciente de 25 anos, com diagnóstico de LAM associada a CET, apresentava história de pneumotórax de repetição e pleurodese havia dois anos. Negava tabagismo e não apresentava história de exposição relevante. Em virtude do acometimento neurológico associado ao CET, a paciente apresentava crises convulsivas frequentes e déficit cognitivo. Apresentava ainda angiomiolipoma renal bilateral de grande volume, além de ter sido anteriormente submetida a nefrectomia parcial direita em virtude de hemorragia. A paciente usava goserelina e doxiciclina desde 2010 e apresentou aumento progressivo do tumor renal nos últimos dois anos. Optou-se por iniciar tratamento com sirolimo, inicialmente na dose de 6 mg/dia, com posterior redução para 2 mg/dia em virtude de náuseas e vômitos. Após 12 meses, observou-se redução significativa do tamanho do angiomiolipoma (de cerca de 20 cm, com massas confluentes, para cerca de 3 cm; Figura 2). Em virtude do déficit cognitivo, a paciente não foi submetida a avaliação funcional pulmonar.


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)

TC de abdome antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando diminuição do volume dos angiomiolipomas renais bilaterais.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f06: TC de abdome antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando diminuição do volume dos angiomiolipomas renais bilaterais.
Mentions: Uma paciente de 25 anos, com diagnóstico de LAM associada a CET, apresentava história de pneumotórax de repetição e pleurodese havia dois anos. Negava tabagismo e não apresentava história de exposição relevante. Em virtude do acometimento neurológico associado ao CET, a paciente apresentava crises convulsivas frequentes e déficit cognitivo. Apresentava ainda angiomiolipoma renal bilateral de grande volume, além de ter sido anteriormente submetida a nefrectomia parcial direita em virtude de hemorragia. A paciente usava goserelina e doxiciclina desde 2010 e apresentou aumento progressivo do tumor renal nos últimos dois anos. Optou-se por iniciar tratamento com sirolimo, inicialmente na dose de 6 mg/dia, com posterior redução para 2 mg/dia em virtude de náuseas e vômitos. Após 12 meses, observou-se redução significativa do tamanho do angiomiolipoma (de cerca de 20 cm, com massas confluentes, para cerca de 3 cm; Figura 2). Em virtude do déficit cognitivo, a paciente não foi submetida a avaliação funcional pulmonar.

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