Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies
Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies
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DOI：
10.1542/peds.2015-3257
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发表时间：
2016-02-01
期刊：
影响因子：
8
通讯作者：
Azizkhan, Richard G.
中科院分区：
文献类型：
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作者：
Adams, Denise M.;Trenor, Cameron C., III;Azizkhan, Richard G.
背景和结论：复杂血管畸形的治疗选择有限，并导致显著的发病率和死亡率。这项II期临床试验招募了复杂血管畸形患者，以确定西罗莫司治疗12个疗程的有效性和安全性;每个疗程定义为28 days.METHODS：治疗包括口服西罗莫司连续给药方案，起始剂量为0.8 mg/m2，每日2次，药代动力学指导的目标血清谷浓度为10 - 15 ng/mL。主要结果是西罗莫司的反应结束时的课程6（根据功能障碍评分，生活质量和放射学评估）和毒性和/或感染相关的死亡率。结果：61例患者入组; 57例可评价疗效的课程6结束时，和53可评价课程12结束时。在疗程6或12结束时，没有患者达到预期的完全缓解。在疗程6结束时，共有47例患者部分缓解，3例患者病情稳定，7例患者病情进展。2例患者因继发于持续不良反应而停用研究药物。西罗莫司导致的3级及以上毒性包括27%患者的血液/骨髓毒性、3%的胃肠道毒性和3%的代谢/实验室毒性。结论：西罗莫司是有效的，耐受性良好，在这些研究患者复杂的血管畸形。在大多数疾病中报告了临床活动。
BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days.METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m(2) per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths.RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred.CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.