1. Hemangiomas
Propranolol in the treatment of infantile hemangiomas: Results from an international randomized, placebo-controlled, multidose, adaptive phase 2/3 study.
C. Leaute-Labreze, J. Mazereeuw-Hautier, L. Guibaud et al.
The study was conducted at the suggestion of the European Medical Association (EMA) and the Food and Drug Administration (FDA) and was an international, multicenter, randomized, double-blind, adaptive phase 2/3 study. The authors presented the results of this study, which was conducted at 56 centers in 24 countries on 460 children aged 1 to 5 months, who were treated for infantile proliferative hemangioma with a pediatric formulation of oral propranolol for 24 weeks.
The purpose of this study was to assess the optimal daily propranolol dosage (3 or 6 mg/kg/day), treatment duration (3 or 6 months), and the superiority of propranolol vs placebo in complete or nearly complete resolution of infantile proliferative hemangiomas. Another parameter assessed was the safety and tolerability of propranolol, especially the cardiovascular, respiratory, metabolic, and behavioral adverse events.
As a result of an interim analysis of the results obtained in the first 188 patients, the 3 mg/kg/day regimen for 6 months was selected for the next step of the study. At the end of the 24-week study, the results in the 55 children treated with placebo and 101 children treated with propranolol were analyzed. A pediatric oral solution of propranolol demonstrated statistically significant efficacy vs placebo (P<0.0001) as complete or nearly complete resolution of infantile proliferative hemangiomas were recorded in 61 patients in the propranolol group (60.4%) compared with only 2 patients in the placebo group (3.6%).
As for tolerability, no unexpected side effects related to propranolol were found. The reported adverse effects were not dose-dependent. Bronchial hyperreactivity and diarrhea occurring in some children were not severe and had no consequences.
This multicenter international study concludes that the new formulation of oral propranolol is effective and well tolerated in the treatment of infantile proliferative hemangioma in children aged 1 to 5 months.
Late recurrences of infantile hemangiomas after propranolol discontinuation.
I. Dreyfus, C. Frisch, A. Maza et al
This paper discusses the characteristics of infantile hemangioma recurrences after the discontinuation of propranolol. This phenomenon is recognized to occur in about 25% of cases within 5 months after discontinuation of the drug, especially when propranolol is not administered until the end of hemangioma growth. The recurrence of hemangioma means its recoloration or increase in size, sometimes exceeding its initial size.
The results of a single-center retrospective study conducted between January 2010 and June 2013 in 29 children with hemangiomas are presented. Children were followed up for at least 8 months after propranolol discontinuation. Treatment with propranolol at doses of 1 to 3 mg/kg/day was started at an average age of 138 days and continued until the average age of 361 days. Sixty-nine percent of hemangiomas were located in the head and neck, and 9 were periocular hemangiomas (67% deep and 33% mixed).
Four hemangioma recurrences were identified, all were deep and located periocularly, and the increase in size after discontinuation of propranolol ranged between 40% and 150% of the initial volume. These cases required therapeutic reintervention.
The authors concluded that these relapses were due to the deep and periocular location of hemangiomas. In these cases, propranolol could reduce or suppress the tumor mass of hemangiomas.
Assessment of the antalgic methods used during treatment with pulsed dye laser (PDL) in infantile flat hemangiomas.
L. Lagier, G. Georgescu, M. Berton et al.
The authors presented the results of a standardized questionnaire on analgesia during pulsed dye laser (PDL) treatment in infantile flat hemangiomas. This questionnaire was filled in by members of the Pediatric research group of the French Society of Dermatology and Laser Group Scientific Committee of the French Society of Dermatology.
The questionnaire contained questions about the use of PDL in private or hospital practice for flat hemangiomas, PDL treatment under general anesthesia, with local anesthetic cream, use of nitrogen oxide, and oral analgesics. There were also questions related to the feeling that these types of anesthesia may or may not reduce the efficacy of PDL therapy for infantile hemangioma.
Responses to the questionnaire show that pain treatment during PDL procedures for hemangioma in children is very heterogeneous. The most commonly used analgesic was an anesthetic cream (56%) with a variable duration of application. However, the effectiveness of anesthetic creams in PDL treatment was not proven by clinical trials and it causes a degree of hemangioma vasoconstriction that may decrease the efficacy of PDL. Fifty-four percent of physicians believe that these anesthetic creams reduce the efficacy of PDL.
The authors concluded that randomized clinical trials are needed to determine the most effective type of anesthesia for PDL in infantile hemangioma.
