Rapamycin for lymphangioleiomyomatosis: optimal timing and optimal dosage

Xu, Kai‐Feng; Tian, Xinlun; Yang, Yanli; Zhang, Hongbing

doi:10.1136/thoraxjnl-2017-211135

Cited by 16 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although sirolimus inhibits tissue proliferation and the release of lymphangiogenic growth factors [8,9], and relieves symptoms, the dyspnea worsened in our case as disease progressed, and lung transplantation was performed at 15 months after the initial operation. The pathology showed the thickened pleura without severe inflammation (Fig.…”

Section: Discussionmentioning

confidence: 67%

Total pleural coverage followed by lung transplantation in patient with lymphangioleiomyomatosis

Kim

Ahn

Son

et al. 2019

Gen Thorac Cardiovasc Surg

View full text Add to dashboard Cite

Tuberous sclerosis complex lymphangioleiomyomatosis (TSC-LAM) is a rare disease, which may develop an intractable pneumothorax. Chemical or mechanical pleurodesis is a general management to prevent recurrence of pneumothorax, rendering it difficult to later dissect the pleura and control intraoperative bleeding. Since total pleural coverage (TPC) alternative to pleurodesis has been firstly reported by Kurihara et al. (Jpn J Thorac Cardiovasc Surg 54:274, 2006), TPC was performed in case of a 46-year-old female with a secondary spontaneous pneumothorax caused by TSC-LAM and followed by lung transplantation. Final pathological report showed the reinforced visceral pleura in the absence of dense adhesions.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

show abstract

Section: Discussionmentioning

confidence: 67%

Total pleural coverage followed by lung transplantation in patient with lymphangioleiomyomatosis

Kim

Ahn

Son

et al. 2019

Gen Thorac Cardiovasc Surg

View full text Add to dashboard Cite

show abstract

“…However, the MILES study [56] suggested that severe LAM patients with higher VEGF-D levels may benefit more from sirolimus treatment. Furthermore, although sirolimus was suggested for application in LAM patients with an annual FEV 1 loss of 90 ml/year (which is threefold higher than the normal FEV 1 loss) in one guideline [1], whether it should be applied in asymptomatic patients with normal or mildly impaired lung function is still unclear [57,58]. Regarding the treatment dosage, Bee et al [9] also found that different serum levels of sirolimus produced similar effects, and lower doses had fewer side effects.…”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of pharmacological treatments for lymphangioleiomyomatosis

et al. 2020

View full text Add to dashboard Cite

Background: Lymphangioleiomyomatosis (LAM) is a rare, low-grade multisystem neoplastic disease. Most LAM patients are at a high risk of losing lung function at an accelerated rate and developing progressive dyspnea. Recently, several studies have reported their experience with pharmacological treatments for LAM. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy and safety of these therapies. Methods: PubMed (Medline), EMBASE, Cochrane Library, Web of Science and EBSCO Host were searched (until March 31, 2019) for eligible prospective studies regarding LAM patients treated with pharmacological treatments. Random effect models were used for quantitative analysis. Results: Fourteen prospective studies regarding five pharmacological treatments (including sirolimus, everolimus, doxycycline, triptorelin, and a combination therapy of sirolimus and hydroxychloroquine) were enrolled in our systematic review, and ten of them were used for the meta-analysis. Seven prospective studies reported that sirolimus was effective at improving or stabilizing lung function and alleviating renal angiomyolipoma (AML) in LAM patients. Subsequent quantitative analyses showed that during sirolimus treatment, the pooled values of lung function and 6-min walk distance (6MWD) were not significantly changed (P > 0.05), with the pooled response rate of AML being 0.62 (95% confidence intervals [CIs]: 0.43 to 0.82, I 2 = 65%). Regarding everolimus, three prospective studies reported similar effects to those of sirolimus with regard to preserving lung function and reducing AMLs. The meta-analysis showed that the changes in lung function during everolimus treatment were not statistically significant (P > 0.05), while the pooled response rate of AML was 0.78 (95% CI: 0.68 to 0.88, I 2 = 8%). Neither the qualitative nor the quantitative results confirmed the benefits of doxycycline or triptorelin treatment, and the effects of the combination therapy were unclear in LAM patients. Most of the adverse events during pharmacological treatments were low or moderate grade and tolerable. Conclusions: Overall, sirolimus and everolimus were recommended for the treatment of LAM because they could stabilize lung function and alleviate renal AML. Doxycycline and triptorelin were not recommended for the treatment of LAM because no beneficial outcomes were consistently observed. The efficacy and safety of combination therapy remain to be further explored.

show abstract

“…The effectiveness of sirolimus includes improvement of lung function, exercise capacity, oxygen level, quality of life, and decrease of VEGF-D level. 77 It may potentially reduce the recurrence of pneumothorax. 78 Sirolimus has been recommended in international guidelines.…”

Section: Sirolimusmentioning

confidence: 99%

“…Dosage adjustment is based on treatment stage (initial or maintenance), complication (chylothorax, angiomyolipomas, pulmonary hypertension, or TSC), treatment response, adverse effects, affordability,and trough blood drug concentration. 77 The recommended trough drug concentration is 5 to 10 ng/mL; however, a lower dose may also be effective.…”

Section: Sirolimusmentioning

confidence: 99%

Lymphangioleiomyomatosis

Liu

et al. 2020

Semin Respir Crit Care Med

Self Cite

View full text Add to dashboard Cite

Lymphangioleiomyomatosis (LAM) is a slow albeit progressive rare neoplastic disease featured with diffuse thin-walled cysts in lungs and angiomyolipomas in kidneys. LAM affects almost exclusively women and has one of the strongest gender predispositions of any extragenital human disease. Two forms of LAM present clinically, sporadic (S-LAM) and tuberous sclerosis complex-associated (TSC-LAM). TSC is an autosomal dominant genetic multisystems neoplastic disease. A high prevalence of LAM can be detected in adult female TSC patients. Tremendous progress has been made in our understanding and management of this rare disease. Both LAM and TSC are TSC2 or TSC1 mutated diseases that result in overactivation of the mechanistic target of rapamycin (mTOR) pathway. Sirolimus, an mTOR inhibitor, has been approved for LAM treatment in the United States and many other countries. Therapies targeting female sex hormones have shown preclinical efficacy in animal and cell culture-based experiments, but have not been properly investigated clinically. In this review, we summarize current recommendations in the diagnosis and treatment of LAM.

show abstract

Rapamycin for lymphangioleiomyomatosis: optimal timing and optimal dosage

Cited by 16 publications

References 20 publications

Total pleural coverage followed by lung transplantation in patient with lymphangioleiomyomatosis

Total pleural coverage followed by lung transplantation in patient with lymphangioleiomyomatosis

The efficacy and safety of pharmacological treatments for lymphangioleiomyomatosis

Lymphangioleiomyomatosis

Contact Info

Product

Resources

About