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Orphanet J Rare Dis. 2018 Oct 29;13(1):191. doi: 10.1186/s13023-018-0934-z.

Sirolimus is efficacious in treatment for extensive and/or complex slow-flow vascular malformations: a monocentric prospective phase II study.

Author information

1
Center for Vascular Anomalies, Institut Roi Albert II, Department of Medical Oncology, Cliniques universitaires Saint Luc, University of Louvain, Brussels, Belgium.
2
Center for Vascular Anomalies, Division of Plastic Surgery, Cliniques universitaires Saint Luc, University of Louvain, 10 avenue Hippocrate, B-1200, Brussels, Belgium.
3
Department of Pediatric Hemato-oncology, Cliniques universitaires Saint Luc, University of Louvain, Brussels, Belgium.
4
Center for Vascular Anomalies, Department of Pediatric Hemato-oncology, Cliniques universitaires Saint Luc, University of Louvain, Brussels, Belgium.
5
Center for Vascular Anomalies, Department of Head and Neck Surgery, Cliniques universitaires Saint-Luc, University of Louvain, Brussels, Belgium.
6
Department of Pediatric Hemato-oncology, CHR Citadelle, Liège, Belgium.
7
Department of Pediatric Cardiology, CHRU Lille, Lille, France.
8
Division of Pediatric Radiology, Cliniques universitaires Saint-Luc, University of Louvain, Brussels, Belgium.
9
Division of Interventional Radiology, Cliniques universitaires Saint-Luc, University of Louvain, Brussels, Belgium.
10
Human Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium.
11
Center for Vascular Anomalies, Division of Plastic Surgery, Cliniques universitaires Saint Luc, University of Louvain, 10 avenue Hippocrate, B-1200, Brussels, Belgium. laurence.boon@uclouvain.be.
12
Human Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium. laurence.boon@uclouvain.be.

Abstract

BACKGROUND:

Extensive and complex vascular malformations often cause chronic pain and severe functional restraint. Conventional treatments, such as surgery and/or sclerotherapy, are rarely curative, underscoring the great need for new therapeutic modalities. Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. The purpose of this prospective study was to assess the efficacy and safety of this treatment in patients with extensive or complex slow-flow vascular malformations.

METHODS:

Sirolimus was administered orally on a continuous dosing schedule with pharmacokinetic-guided target serum concentration level of 10 to 15 ng/ml. Patients were seen every month for the first three months and subsequently every three months. The primary endpoints were safety and efficacy, based on clinical, biological and radiological evaluations, as well as a quality of life questionnaire.

RESULTS:

Nineteen patients, from 3 to 64 years old, with lymphatic (LM), venous (VM) or complex slow-flow malformations, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, 16 patients were available for assessment of efficacy and safety: all had a significant and rapid improvement of their symptoms and quality of life. In two patients, sirolimus treatment permitted sclerotherapy and surgery, initially evaluated unfeasible. Sirolimus was well tolerated, with mucositis as the most common (10% of patients) grade 3 adverse event.

CONCLUSIONS:

Sirolimus was efficient in extensive LM, VM and/or complex malformations that were refractory to conventional treatments and was well tolerated.

KEYWORDS:

Complex vascular malformation; Extensive vascular anomaly; Lymphatic malformation; Rapamycin; Sirolimus; Slow-flow anomaly; Venous malformation

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