Gore Lia, Chawla Sant, Petrilli Antonio, Hemenway Molly, Schissel Debra, Chua Vickey, Carides Alexandra D, Taylor Arlene, Devandry Suzanne, Valentine Jack, Evans Judith K, Oxenius Bettina
Division of Pediatric Hematology/Oncology/Bone Marrow Transplant, Children's Hospital and The University of Colorado Denver, Aurora, Colorado, USA.
Pediatr Blood Cancer. 2009 Feb;52(2):242-7. doi: 10.1002/pbc.21811.
The neurokinin-1 receptor antagonist aprepitant, plus a 5HT3 antagonist and corticosteroid is well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in adults but has not been formally assessed in adolescents.
Patients age 11-19 years old receiving emetogenic chemotherapy were randomized 2:1 to aprepitant triple therapy (aprepitant [A] 125 mg p.o., dexamethasone [D] 8 mg p.o., and ondansetron [O] 0.15 mg/kg i.v. t.i.d. day 1; A 80 mg, D 4 mg, and O 0.15 mg/kg t.i.d. day 2; A 80 mg and D 4 mg day 3; and D 4 mg day 4) or a control regimen (D 16 mg and O 0.15 mg/kg t.i.d. day 1; D 8 mg and O 0.15 mg/kg t.i.d. day 2; and D 8 mg days 3 and 4). The primary endpoint was the difference in drug-related adverse events during and for 14 days following treatment. Efficacy and aprepitant pharmacokinetics were assessed.
Baseline characteristics were similar between aprepitant (N = 28) and control (N = 18) groups. Febrile neutropenia was more frequent in the aprepitant group (25% vs. 11.1%). Complete response (CR) rates were 35.7% for aprepitant triple therapy versus 5.6% for the control group. Mean plasma aprepitant AUC(0-24 hr) and C(max) on day 1 and mean trough concentrations on days 2 and 3 were consistently lower compared to historical data obtained from healthy adults; however, the differences were not clinically significant.
Aprepitant triple therapy was generally well tolerated; CR were greater with aprepitant, although not statistically significant. Pharmacokinetics suggest that the adult dosing regimen is appropriate for adolescents.
神经激肽 -1 受体拮抗剂阿瑞匹坦联合 5 -羟色胺 3 受体拮抗剂及糖皮质激素在预防成人化疗引起的恶心和呕吐方面耐受性良好且有效，但尚未在青少年中进行正式评估。
年龄在 11 - 19 岁接受致吐性化疗的患者按 2:1 随机分组，接受阿瑞匹坦三联疗法（第 1 天：阿瑞匹坦[A]口服 125 mg、地塞米松[D]口服 8 mg、昂丹司琼[O]静脉注射 0.15 mg/kg，每日 3 次；第 2 天：A 80 mg、D 4 mg、O 0.15 mg/kg，每日 3 次；第 3 天：A 80 mg、D 4 mg；第 4 天：D 4 mg）或对照方案（第 1 天：D 16 mg、O 0.15 mg/kg，每日 3 次；第 2 天：D 8 mg、O 0.15 mg/kg，每日 3 次；第 3 天和第 4 天：D 8 mg）。主要终点是治疗期间及治疗后 14 天内药物相关不良事件的差异。评估了疗效和阿瑞匹坦的药代动力学。
阿瑞匹坦组（N = 28）和对照组（N = 18）的基线特征相似。阿瑞匹坦组发热性中性粒细胞减少更为常见（25%对 11.1%）。阿瑞匹坦三联疗法的完全缓解（CR）率为 35.7%，而对照组为 5.6%。与从健康成年人获得的历史数据相比，第 1 天的平均血浆阿瑞匹坦 AUC(0 - 24 小时)和 C(max)以及第 2 天和第 3 天的平均谷浓度持续较低；然而，差异无临床意义。
阿瑞匹坦三联疗法总体耐受性良好；阿瑞匹坦组完全缓解率更高，尽管无统计学意义。药代动力学表明成人给药方案适用于青少年。
