title: Efficacy and Safety of Mammalian Target of Rapamycin Inhibitors in Vascular Anomalies: A Systematic Review.
abstract: Mammalian target of rapamycin (mTOR) inhibitors are a promising new treatment in vascular anomalies, but no published randomized controlled trials are available. The aim of this systematic review of all reported cases was to assess the efficacy and safety of mTOR inhibitors in all vascular anomalies, except cancers, in children and adults. In November 2014 MEDLINE, CENTRAL, LILACS and EMBASE were searched for studies of mTOR inhibitors in any vascular condition, except for malignant lesions, in humans. Fourteen publications and 9 posters, with data on 25 and 59 patients, respectively, all < 18 years old were included. Of these patients, 35.7% (n = 30) had vascular tumours, and 64.3% (n = 54) had malformations. Sirolimus was the most frequent mTOR inhibitor used (98.8%, n = 83). It was efficient in all cases, at a median time of 2 weeks (95% confidence interval 1-10 weeks). Sirolimus was well tolerated, the main side-effect being mouth sores, which led to treatment withdrawal in one case. The dosage of sirolimus was heterogeneous, the most common being 1.6 mg/m2/day.
authors.affiliation: Department of Dermatology, University François Rabelais Tours, CHRU Tours, FR-37044 Tours, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Nadal
authors.forename: Bruno
authors.initials: B
authors.lastname: Giraudeau
authors.forename: Elsa
authors.initials: E
authors.lastname: Tavernier
authors.forename: Annie-Pierre
authors.initials: AP
authors.lastname: Jonville-Bera
authors.forename: Gerárd
authors.initials: G
authors.lastname: Lorette
authors.forename: Annabel
authors.initials: A
authors.lastname: Maruani
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome; D054079:Vascular Malformations / Q000188:drug therapy* / Q000201:enzymology; D019043:Vascular Neoplasms / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases