Yi Ji1, Siyuan Chen2, Kaiying Yang3, Jiangyuan Zhou3, Xuepeng Zhang2, Xian Jiang4, Xuewen Xu5, Guoyan Lu6, Liqing Qiu7, Feiteng Kong8, Yongbo Zhang9. 1. Division of Oncology, Department of Pediatric Surgery, West China Second University Hospital, Sichuan University, Chengdu, China. Electronic address: jijiyuanyuan@163.com. 2. Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Second University Hospital, Sichuan University, Chengdu, China. 3. Division of Oncology, Department of Pediatric Surgery, West China Second University Hospital, Sichuan University, Chengdu, China. 4. Department of Dermatology, West China Second University Hospital, Sichuan University, Chengdu, China. 5. Department of Burn and Plastic Surgery, West China Second University Hospital, Sichuan University, Chengdu, China. 6. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China. 7. Department of Pediatric Surgery, Chengdu Shangjin Nanfu Hospital, Chengdu, China. 8. Department of Pediatric Surgery, Sichuan Women and Children's Hospital, Chengdu, China. 9. Department of Pediatric Surgery, Chengdu Women and Children's Central Hospital, Chengdu, China.
Abstract
OBJECTIVE: Complicated vascular anomalies (VAs) can be intractable and uncontrollable using conventional treatment and can result in lethal outcomes. We undertook a prospective, multicenter phase II trial to evaluate the efficacy and safety of sirolimus in pediatric patients with complicated VAs. METHODS: Eligible patients were required to be aged 0 to 14 years and to have a complicated VA. The patients were treated with daily oral sirolimus for 12 months. The primary endpoint was the response, which was measured using sequential volumetric magnetic resonance imaging. The secondary endpoints were the disease severity score and quality of life. RESULTS: Of 126 patients enrolled on an intention-to-treat basis, 98 (77.8%) had had an objective response to sirolimus, with a ≥20% decrease in lesion volume. Compared with those with arteriovenous malformations, the response rates were higher (>80%) for patients with common lymphatic malformations, venous malformations, kaposiform hemangioendothelioma, and combined malformations with a prominent venous and/or lymphatic component (P < .05). Improvements in the disease severity score and quality of life were obtained in 83.3% and 79.4% of patients, respectively. The most common adverse event was mucositis in 47 patients. More serious adverse events included reversible grade 4 pneumonitis in 3 patients and grade 4 upper respiratory infection in 1 patient. All these adverse events were considered at least possibly related to the treatment. CONCLUSIONS: Sirolimus is an apparently effective option for pediatric patients with various types of complicated VAs. Close monitoring of possible adverse events is required. The results from the present trial are the basis for future prospective studies using new therapeutic approaches.
OBJECTIVE: Complicated vascular anomalies (VAs) can be intractable and uncontrollable using conventional treatment and can result in lethal outcomes. We undertook a prospective, multicenter phase II trial to evaluate the efficacy and safety of sirolimus in pediatric patients with complicated VAs. METHODS: Eligible patients were required to be aged 0 to 14 years and to have a complicated VA. The patients were treated with daily oral sirolimus for 12 months. The primary endpoint was the response, which was measured using sequential volumetric magnetic resonance imaging. The secondary endpoints were the disease severity score and quality of life. RESULTS: Of 126 patients enrolled on an intention-to-treat basis, 98 (77.8%) had had an objective response to sirolimus, with a ≥20% decrease in lesion volume. Compared with those with arteriovenous malformations, the response rates were higher (>80%) for patients with common lymphatic malformations, venous malformations, kaposiform hemangioendothelioma, and combined malformations with a prominent venous and/or lymphatic component (P < .05). Improvements in the disease severity score and quality of life were obtained in 83.3% and 79.4% of patients, respectively. The most common adverse event was mucositis in 47 patients. More serious adverse events included reversible grade 4 pneumonitis in 3 patients and grade 4 upper respiratory infection in 1 patient. All these adverse events were considered at least possibly related to the treatment. CONCLUSIONS: Sirolimus is an apparently effective option for pediatric patients with various types of complicated VAs. Close monitoring of possible adverse events is required. The results from the present trial are the basis for future prospective studies using new therapeutic approaches.