■难治性淋巴异常(LA)包括囊性淋巴畸形(LM;大囊性,微囊,或混合),全身淋巴异常,和Gorham-Stout病.LA可以表现出严重的症状和不良的预后。因此,有必要对治疗进行前瞻性研究.我们进行了西罗莫司治疗顽固性LAs的前瞻性临床试验。
■这是一个开放标签,单臂,多中心,涉及日本五个机构的前瞻性试验。所有患有LA的患者每天一次口服西罗莫司,并调整剂量以确保谷浓度保持在5-15ng/mL内。我们前瞻性评估了药物反应(靶病变放射性体积变化的反应率),性能状态,呼吸功能的变化,内脏损伤(胸腔积液,腹水,出血,疼痛),实验室检查数据,生活质量(QOL),和安全性在12、24和52周的给药。
■11例LAs患者(9例全身淋巴异常,1囊性LM,1Gorham-Stout病)用西罗莫司治疗,其中6人(54.5%;95%置信区间:23.4-83.3%)在给药52周时在放射学检查中表现出部分反应。没有患者达到完全缓解。在给药12周和24周时,8例患者(72.7%)已经显示出部分反应。然而,病情稳定的患者在12周后表现为轻微或无减少.不良事件,如口腔炎,痤疮样皮炎,腹泻,发烧,与西罗莫司很常见。西罗莫司是安全和耐受的。
■西罗莫司可以减少LA中的淋巴组织体积,并可能导致临床症状和生活质量的改善。
UNASSIGNED: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs.
UNASSIGNED: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5-15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration.
UNASSIGNED: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham-Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4-83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable.
UNASSIGNED: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.