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Table 1 Characteristics of the included studies

From: The efficacy and safety of pharmacological treatments for lymphangioleiomyomatosis

Author, Publication Year, CountryJournalStudy designDiagnosis,
No. of patients
Study durationIntervention and sample sizeTreatment regimenStudy outcomes
Bissler [24] (2008) USAN Engl J MedSingle-center, nonrandomized open-label phase 1–2 trialLAM (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 areaRenal AMLs, lung function, lung cyst volume, 6MWD, AEs, neurologic assessment.
Harari [20] (2008) ItalyChestSingle-center, prospective phase 1 trialLAM (n = 11)3 years of treatmentTriptorelin (n = 11)11.25 mg IMHormonal assays, pulmonary function tests, 6MWD, bone mineral density.
Dabora [34] (2011) USAPLoS ONEMulticenter open-label, phase 2 trial, single-armTSC-LAM
(n = 21),
TSC (n = 15)
1 year of treatmentSirolimus (n = 36)2 mg/dayAMLs, kidney cysts, skin lesions, pulmonary function, VEGF-D.
McCormack [33] (2011) USAN Engl J MedMulticenter, randomized, placebo-controlled studyLAM (n = 81),
TSC-LAM (n = 8)
1 year of treatment,
1 year of observation
Sirolimus group
(n = 46);
Placebo group
(n = 43)
2 mg/dayLung function, 6MWD, VEGF-D, QOL scores, AEs.
Davies [35] (2011) UKClin Cancer ResMulticenter nonrandomized open label phase 2 trialLAM (n = 6),
TSC-LAM (n = 3),
TSC (n = 7),
2 years of treatmentSirolimus (n = 16)0.5 mg/m2 body-surface areaRenal AMLs, lung function, AEs and neurocognitive function.
Bissler [25] (2013) USALancetMulticenter, randomized, double-blind, placebo-controlled phase 3 trialLAM (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/dayAMLs, skin lesion, pharmacokinetics of everolimus, pulmonary function, AEs, neuropsychological assessments, VEGF-D.
Piment a[22] (2013) BrazilJ Bras PneumolSingle-center open-label, single-arm, interventional clinical trialLAM (n = 31)1 year of treatmentDoxycycline (n = 31)100 mg/dayPulmonary function, 6MWD, QOL, MMP-2, MMP-9, VEGF-D
Chang [23] (2014) UKEur Respir JSingle-center randomized placebo-controlled trialLAM (n = 23)2 years of treatmentDoxycycline group (n = 12);
Placebo group (n = 11)
100 mg/day for 3 months followed by 200 mg/day for 21 monthsLung function, exercise capacity, QOL, shuttle walk distance, MMP levels, VEGF-D.
Goldberg [36] (2015) USAEur Respir JMulticenter, open-label, nonrandomized, phase 2 trialLAM (n = 19),
TSC-LAM
(n = 5),
Treatment for 26 weeksEverolimus (n = 24)2.5 mg/day for 4 weeks, 5 mg/day for 4 weeks, 10 mg/day for 18 weeksLung function, VEGF-D, 6MWD, everolimus pharmacokinetics, AEs.
Takada [37] (2016) JapanAnn Am Thorac SocMulticenter, single-arm, open-label trialLAM and TSC-LAM (n = 63)2 years of treatmentSirolimus (n = 63)2 mg/dayLung function, QOL scores, AEs
EI-Chemaly [38] (2017) USAChestTwo-center phase 1 trialLAM (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, CountryJournalStudy designDiagnosis,
No of patients
Study durationIntervention and sample sizeTreatment regimenStudy outcomes
Bee [9] (2018)
UK
ThoraxA prospective national cohort, single-arm study,LAM (n = 38),
TSC-LAM
(n = 9)
35.8 ± 18 months of treatmentSirolimus (n = 47)1–2 mg/dayLung function, VEGF-D, AEs.
Cai [39] (2018) ChinaOrphanet J Rare DisSingle-center, nonrandomized, open-label phase 2 trialTSC-LAM (n = 6),
TSC (n = 12)
1 year of treatment
1 year of observation
Everolimus (n = 18)10 mg/dayAMLs, skin lesions, lung function, AEs.
Aghaeimeybodi [40] (2019) IranCaspian J Intern MedA prospective phase 1 trialLAM (n = 2),
TSC-LAM (n = 4)
1 year of treatmentSirolimus (n = 6)2 mg/dayLung function, 6MWD, AEs.
  1. The general information of the included studies, including: name of the first author, publication year, study location, name of the journal, study design, number and diagnosis of patients, study duration, intervention and sample size of it, treatment regimen, and outcome indicator type for each study
  2. LAM lymphangioleiomyomatosis, TSC tuberous sclerosis complex, AML angiomyolipomas, 6MWD 6-min walk distance, AEs adverse events, IM Intramuscular injection, VEGF-D vascular endothelial growth factor D, QOL quality of life, MMP matrix metalloproteinase