Ozeki Michio, Endo Saori, Yasue Shiho, Asada Ryuta, Saito Akiko M, Hashimoto Hiroya, Ueno Shigeru, Watanabe Shoji, Kato Motoi, Deie Kyoichi, Nosaka Shunsuke, Miyasaka Mikiko, Umezawa Akihiro, Matsuoka Kentaro, Kato Mototoshi, Kuroda Tatsuo, Maekawa Takanobu, Hirakawa Satoshi, Furukawa Taizo, Fumino Shigehisa, Tajiri Tatsuro, Takemoto Junkichi, Kawakubo Naonori, Fujino Akihiro
Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
Clinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan.
Pediatr Int. 2025 Jan-Dec;67(1):e70002. doi: 10.1111/ped.70002.
Intractable vascular anomalies (VAs), including vascular tumors and venous, lymphatic, and mixed malformations, often have severe symptoms and a poor prognosis, highlighting the need for new treatments. We conducted a prospective trial of sirolimus (tablet and granule forms) for the treatment of VAs.
In this open-label, single-arm, multicenter trial across four Japanese institutions, patients with VAs received oral sirolimus daily, targeting a trough concentration of 5-15 ng/mL. We evaluated response rates (radiological volume changes in lesions), skin lesions, performance status, respiratory function, visceral symptoms (bleeding, pain), laboratory data, quality of life, and safety at 12, 24, and 52 weeks.
Thirteen patients with VAs were treated with sirolimus. Seven patients (53.8%; 95% confidence interval: 25.1%-80.8%) showed a partial radiological response at 24 weeks, with no complete responses, and 61.5% had a partial response by 12 weeks, with little subsequent change in patients who had stable disease thereafter. Improvements in skin lesions, blood coagulation, and activities of daily living were noted. Common adverse events included stomatitis, dermatitis, diarrhea, and fever.
Sirolimus may reduce VA tissue volume and potentially improve symptoms and activities of daily living in patients with VAs.
难治性血管异常（VAs），包括血管肿瘤以及静脉、淋巴和混合性畸形，通常具有严重症状且预后较差，这凸显了对新治疗方法的需求。我们开展了一项关于西罗莫司（片剂和颗粒剂）治疗VAs的前瞻性试验。
在这项在日本四个机构进行的开放标签、单臂、多中心试验中，VAs患者每日口服西罗莫司，目标谷浓度为5 - 15 ng/mL。我们在12周、24周和52周时评估了缓解率（病变的放射学体积变化）、皮肤病变、功能状态、呼吸功能、内脏症状（出血、疼痛）、实验室数据、生活质量和安全性。
13例VAs患者接受了西罗莫司治疗。7例患者（53.8%；95%置信区间：25.1% - 80.8%）在24周时出现部分放射学缓解，无完全缓解，61.5%的患者在12周时出现部分缓解，此后病情稳定的患者变化不大。观察到皮肤病变、凝血和日常生活活动有所改善。常见不良事件包括口腔炎、皮炎、腹泻和发热。
西罗莫司可能会减少VAs患者的组织体积，并有可能改善其症状和日常生活活动能力。
