A phase I trial and pharmacokinetic study of a 24-hour infusion of trabectedin (Yondelis®, ET-743) in children and adolescents with relapsed or refractory solid tumors.
A phase I trial and pharmacokinetic study of a 24-hour infusion of trabectedin (Yondelis®, ET-743) in children and adolescents with relapsed or refractory solid tumors.
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DOI：
10.1002/pbc.24201
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发表时间：
2012-11
影响因子：
3.2
通讯作者：
Fox, Elizabeth
中科院分区：
文献类型：
--
作者：
Chuk, Meredith K.;Aikin, Alberta;Whitcomb, Trish;Widemann, Brigitte C.;Zannikos, Peter;Bayever, Eliel;Balis, Frank M.;Fox, Elizabeth
这项 I 期研究的目的是确定对患有难治性或复发性实体瘤的儿童和青少年进行 24 小时连续静脉输注曲贝替定的最大耐受剂量 (MTD)、毒性特征和药代动力学。年龄在 4 岁至 16 岁之间的难治性实体瘤患者每 21 天接受一次 24 小时输注曲贝替定。每个周期均给予地塞米松和预防性生长因子支持。在第 1 周期进行药代动力学研究。中位（范围）年龄 14.5（8-16）岁的患者（n=12）接受 1.1（n=3）、1.5（n=6）或 1.7（n=3）mg/m2 剂量的曲贝替定。在 1.5 mg/m2 剂量水平下，一名患者出现剂量限制性厌食和疲劳。在 1.7 mg/m2 剂量下，2 名患者出现剂量限制性毒性、脱水和 γ-谷氨酰转肽酶 (GGT) 升高。非剂量限制性毒性包括血清转氨酶升高、骨髓抑制、恶心、呕吐和疲劳。血浆药代动力学参数与成人的历史数据相似。在一名神经内分泌癌患者中观察到部分缓解（PR）。 3 名患者达到疾病稳定 (SD)（≥6 个周期）（骨肉瘤 n=2，促结缔组织增生性小圆细胞肿瘤 n=1）。曲贝替定在难治性实体瘤儿科患者中的 MTD 为每 21 天 24 小时内静脉注射 1.5 mg/m2。需要地塞米松改善肝毒性和预防性生长因子支持。
The objectives of this phase I study were to determine the maximum tolerated dose (MTD), toxicity profile and pharmacokinetics of a 24-hour continuous intravenous infusion of trabectedin administered to children and adolescents with refractory or relapsed solid tumors. Patients between the ages of 4 and 16 years old with refractory solid tumors received trabectedin as a 24-hour infusion every 21 days. Dexamethasone and prophylactic growth factor support were administered with each cycle. Pharmacokinetic studies were conducted during cycle 1. Patients (n=12) median (range) age 14.5 (8–16) years received trabectedin at 1.1 (n=3), 1.5 (n=6) or 1.7 (n=3) mg/m2. At the 1.5 mg/m2 dose level, one patient had dose limiting anorexia and fatigue. At 1.7 mg/m2, 2 patients experienced dose limiting toxicity, dehydration and gamma-glutamyl transpeptidase (GGT) elevation. Non-dose limiting toxicities included elevated serum transaminases, myelosuppression, nausea, emesis and fatigue. Plasma pharmacokinetic parameters were similar to historical data in adults. One partial response (PR) was observed in a patient with neuroendocrine carcinoma. Stable disease (SD) (≥6 cycles) was achieved in 3 patients (osteosarcoma n=2, desmoplastic small round cell tumor n=1). The MTD of trabectedin in pediatric patients with refractory solid tumors is 1.5 mg/m2 IV over 24 hours every 21 days. Dexamethasone to ameliorate hepatic toxicity and prophylactic growth factor support are required.
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影响因子：
45.3
作者：
Garcia-Carbonero, R;Supko, JG;Demetri, GD
通讯作者：
Demetri, GD
影响因子：
45.3
作者：
Demetri, George D.;Chawla, Sant P.;Le Cesne, Axel
通讯作者：
Le Cesne, Axel
影响因子：
82.9
作者：
Takebayashi, Y;Pourquier, P;Pommier, Y
通讯作者：
Pommier, Y
影响因子：
51.1
作者：
Grosso, Federica;Jones, Robin L.;Casali, Paola G.
通讯作者：
Casali, Paola G.
影响因子：
2.3
作者：
Stokvis, E;Rosing, H;Beijnen, JH
通讯作者：
Beijnen, JH