Patients with Congenital Low-Flow Vascular Malformation Treated with Low Dose Sirolimus

Autor: D. Maroeska W.M. te Loo, Willemijn M. Klein, Gerard A. Rongen, Veroniek E M Harbers, Chantal M.A.M. van der Horst, Bas H. Verhoeven, Leo J. Schultze Kool, Peter C. J. de Laat, Carine J.M. van der Vleuten
Přispěvatelé: Pediatrics, Plastic, Reconstructive and Hand Surgery, ACS - Atherosclerosis & ischemic syndromes, AMS - Musculoskeletal Health, AMS - Rehabilitation & Development, ACS - Diabetes & metabolism
Rok vydání: 2021
Předmět:
030213 general clinical medicine
Pediatrics
medicine.medical_specialty
Adolescent
mTOR inhibitor
Vascular Malformations
Visual analogue scale
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
Pain
Vascular malformation
Placebo
Venous malformation
03 medical and health sciences
0302 clinical medicine
Quality of life
medicine
Humans
Case Series
Pharmacology (medical)
Lymphatic malformation
cardiovascular diseases
Adverse effect
Protein Kinase Inhibitors
Sirolimus
business.industry
Other Research Radboud Institute for Health Sciences [Radboudumc 0]
Common Terminology Criteria for Adverse Events
General Medicine
medicine.disease
equipment and supplies
Low dose sirolimus
Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10]
Treatment Outcome
surgical procedures
operative
030220 oncology & carcinogenesis
Quality of Life
cardiovascular system
Female
business
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
medicine.drug
Zdroj: Advances in Therapy, 38, 3465-3482
Advances in Therapy
Advances in Therapy, 38(6), 3465-3482. Springer International Publishing AG
Advances in therapy, 38(6), 3465-3482. Health Communications Inc.
Advances in Therapy, 38, 6, pp. 3465-3482
ISSN: 0741-238X
Popis: Introduction Patients with congenital vascular malformations often suffer from an impaired quality of life (QoL) because of pain and functional disabilities. Previous studies have shown that the mTOR inhibitor sirolimus can reduce complaints and improve QoL in some patients. High target levels of sirolimus of 10–15 ng/ml were well tolerated; however, in a relative high percentage of patients sirolimus caused serious adverse events (AEs). Methods A case series of 12 patients with therapy-resistant low-flow vascular malformations was treated with sirolimus, using low target levels of 4–10 ng/ml. Efficacy of sirolimus was evaluated in regard to pain symptoms using the visual analogue scale/numeric rating scale and patients reported QoL. To rule out a placebo effect of sirolimus, sirolimus was stopped after a certain time point and reintroduced as soon as complaints returned. Adverse events were closely monitored and graded using the Common Terminology Criteria for Adverse Events (CTCAE) grading. Results An improvement in symptoms was seen in 92% (n = 11/12) of patients. In nine patients pain complaints returned. Seven out of nine of them (78%) again experienced a reduction of symptoms after restarting sirolimus treatment. Despite low target levels, these response rates are comparable to those found in the literature using higher target levels of sirolimus. However, significantly less serious AEs were observed with low dose sirolimus, suggesting low dose sirolimus might be safer. Unfortunately, young adolescent female patients developed serious menstrual disturbances during treatment with low dose sirolimus. We describe this adverse event for the first time in patients with congenital vascular malformations and this might be specifically related to low dose sirolimus. Conclusions Low dose sirolimus showed a high efficacy in patients with therapy-resistant and low-flow malformation, with a lower incidence of serious adverse events. At the same time a new adverse event, namely menstrual cycle disturbance, was observed in young adolescents, indicating the need for caution when sirolimus is given. This is extremely relevant to patients with low-flow vascular malformation, who are likely to require lifelong treatment for their condition. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01758-y.
Databáze: OpenAIRE
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