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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

Radiografia de tórax antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando a resolução do quilotórax.
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f05: Radiografia de tórax antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando a resolução do quilotórax.

Mentions: Uma paciente de 48 anos, tabagista (com carga tabágica de 15 anos-maço) foi internada com história de dispneia havia dois anos, com piora havia uma semana. Negava outras doenças. A paciente relatou que fora submetida a ooforectomia havia nove anos em virtude de um tumor benigno e a nefrectomia direita havia 6 meses em virtude de angiomiolipoma renal. Não apresentava história de exposição relevante. O exame físico revelou que a paciente estava emagrecida, com murmúrio vesicular abolido em todo o hemitórax direito e SpO2 de 92% em ar ambiente. A radiografia de tórax revelou derrame pleural volumoso à direita (Figura 1). A paciente foi submetida a toracocentese, confirmando-se o diagnóstico de quilotórax. A prova de função pulmonar realizada após a drenagem revelou CVF de 3,12 l (100% do previsto), VEF1 de 1,95 l (75% do previsto), VEF1/CVF de 0,62, CPT de 5,27 l (92% do previsto) e DLCO de 15,41 ml/min/mmHg (65% do previsto; Tabela 1). A TC de tórax revelou cistos pulmonares difusos com paredes regulares. A paciente apresentou piora da dispneia e quilotórax de difícil manejo, mantendo-se um alto débito de drenagem a despeito do tratamento com nutrição parenteral total. Optou-se por iniciar tratamento com sirolimo (1 mg/dia). Observou-se resolução do quilotórax e estabilidade funcional após 12 meses de tratamento (Figura 1 e Tabela 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)

Radiografia de tórax antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando a resolução do quilotórax.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f05: Radiografia de tórax antes do tratamento com sirolimo (em A) e após 12 meses de tratamento com o medicamento (em B), mostrando a resolução do quilotórax.
Mentions: Uma paciente de 48 anos, tabagista (com carga tabágica de 15 anos-maço) foi internada com história de dispneia havia dois anos, com piora havia uma semana. Negava outras doenças. A paciente relatou que fora submetida a ooforectomia havia nove anos em virtude de um tumor benigno e a nefrectomia direita havia 6 meses em virtude de angiomiolipoma renal. Não apresentava história de exposição relevante. O exame físico revelou que a paciente estava emagrecida, com murmúrio vesicular abolido em todo o hemitórax direito e SpO2 de 92% em ar ambiente. A radiografia de tórax revelou derrame pleural volumoso à direita (Figura 1). A paciente foi submetida a toracocentese, confirmando-se o diagnóstico de quilotórax. A prova de função pulmonar realizada após a drenagem revelou CVF de 3,12 l (100% do previsto), VEF1 de 1,95 l (75% do previsto), VEF1/CVF de 0,62, CPT de 5,27 l (92% do previsto) e DLCO de 15,41 ml/min/mmHg (65% do previsto; Tabela 1). A TC de tórax revelou cistos pulmonares difusos com paredes regulares. A paciente apresentou piora da dispneia e quilotórax de difícil manejo, mantendo-se um alto débito de drenagem a despeito do tratamento com nutrição parenteral total. Optou-se por iniciar tratamento com sirolimo (1 mg/dia). Observou-se resolução do quilotórax e estabilidade funcional após 12 meses de tratamento (Figura 1 e Tabela 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