Background
Methods
Search strategy
Inclusion criteria and exclusion criteria
Data extraction
Quality assessment
Data synthesis and statistical analysis
Results
Search results and characteristics of the included studies
Author, Publication Year, Country | Journal | Study design | Diagnosis, No. of patients | Study duration | Intervention and sample size | Treatment regimen | Study outcomes |
---|---|---|---|---|---|---|---|
Bissler [24] (2008) USA | N Engl J Med | Single-center, nonrandomized open-label phase 1–2 trial | LAM (n = 6), TSC-LAM (n = 12), TSC (n = 7), | 1 year of treatment, 1 year of observation | Sirolimus (n = 25) | 0.25 mg/m2 body-surface area | Renal AMLs, lung function, lung cyst volume, 6MWD, AEs, neurologic assessment. |
Harari [20] (2008) Italy | Chest | Single-center, prospective phase 1 trial | LAM (n = 11) | 3 years of treatment | Triptorelin (n = 11) | 11.25 mg IM | Hormonal assays, pulmonary function tests, 6MWD, bone mineral density. |
Dabora [34] (2011) USA | PLoS ONE | Multicenter open-label, phase 2 trial, single-arm | TSC-LAM (n = 21), TSC (n = 15) | 1 year of treatment | Sirolimus (n = 36) | 2 mg/day | AMLs, kidney cysts, skin lesions, pulmonary function, VEGF-D. |
McCormack [33] (2011) USA | N Engl J Med | Multicenter, randomized, placebo-controlled study | LAM (n = 81), TSC-LAM (n = 8) | 1 year of treatment, 1 year of observation | Sirolimus group (n = 46); Placebo group (n = 43) | 2 mg/day | Lung function, 6MWD, VEGF-D, QOL scores, AEs. |
Davies [35] (2011) UK | Clin Cancer Res | Multicenter nonrandomized open label phase 2 trial | LAM (n = 6), TSC-LAM (n = 3), TSC (n = 7), | 2 years of treatment | Sirolimus (n = 16) | 0.5 mg/m2 body-surface area | Renal AMLs, lung function, AEs and neurocognitive function. |
Bissler [25] (2013) USA | Lancet | Multicenter, randomized, double-blind, placebo-controlled phase 3 trial | LAM (n = 5), TSC-LAM (n = 24), TSC (n = 89) | Median 38 weeks for everolimus; median 34 weeks for placebo. | Everolimus group (n = 79); Placebo group (n = 39) | 10 mg/day | AMLs, skin lesion, pharmacokinetics of everolimus, pulmonary function, AEs, neuropsychological assessments, VEGF-D. |
Piment a[22] (2013) Brazil | J Bras Pneumol | Single-center open-label, single-arm, interventional clinical trial | LAM (n = 31) | 1 year of treatment | Doxycycline (n = 31) | 100 mg/day | Pulmonary function, 6MWD, QOL, MMP-2, MMP-9, VEGF-D |
Chang [23] (2014) UK | Eur Respir J | Single-center randomized placebo-controlled trial | LAM (n = 23) | 2 years of treatment | Doxycycline group (n = 12); Placebo group (n = 11) | 100 mg/day for 3 months followed by 200 mg/day for 21 months | Lung function, exercise capacity, QOL, shuttle walk distance, MMP levels, VEGF-D. |
Goldberg [36] (2015) USA | Eur Respir J | Multicenter, open-label, nonrandomized, phase 2 trial | LAM (n = 19), TSC-LAM (n = 5), | Treatment for 26 weeks | Everolimus (n = 24) | 2.5 mg/day for 4 weeks, 5 mg/day for 4 weeks, 10 mg/day for 18 weeks | Lung function, VEGF-D, 6MWD, everolimus pharmacokinetics, AEs. |
Takada [37] (2016) Japan | Ann Am Thorac Soc | Multicenter, single-arm, open-label trial | LAM and TSC-LAM (n = 63) | 2 years of treatment | Sirolimus (n = 63) | 2 mg/day | Lung function, QOL scores, AEs |
EI-Chemaly [38] (2017) USA | Chest | Two-center phase 1 trial | LAM (n = 13) | 24 weeks of treatment, 24 weeks of observation | Hydroxychloroquine and sirolimus (n = 13) | Hydroxychloroquine (200 mg or 400 mg) Sirolimus (2 mg/day) | Lung function, 6MWD, QOL, AMLs, VEGF-D, AEs. |
Author, Publication Year, Country | Journal | Study design | Diagnosis, No of patients | Study duration | Intervention and sample size | Treatment regimen | Study outcomes |
Bee [9] (2018) UK | Thorax | A prospective national cohort, single-arm study, | LAM (n = 38), TSC-LAM (n = 9) | 35.8 ± 18 months of treatment | Sirolimus (n = 47) | 1–2 mg/day | Lung function, VEGF-D, AEs. |
Cai [39] (2018) China | Orphanet J Rare Dis | Single-center, nonrandomized, open-label phase 2 trial | TSC-LAM (n = 6), TSC (n = 12) | 1 year of treatment 1 year of observation | Everolimus (n = 18) | 10 mg/day | AMLs, skin lesions, lung function, AEs. |
Aghaeimeybodi [40] (2019) Iran | Caspian J Intern Med | A prospective phase 1 trial | LAM (n = 2), TSC-LAM (n = 4) | 1 year of treatment | Sirolimus (n = 6) | 2 mg/day | Lung function, 6MWD, AEs. |