Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins αvβ3 and αvβ5 in patients with advanced solid tumours
Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins αvβ3 and αvβ5 in patients with advanced solid tumours
复制标题
DOI：
10.1016/s0959-8049(03)00057-1
复制
发表时间：
2003-05-01
影响因子：
8.4
通讯作者：
van Oosterom, AT
中科院分区：
文献类型：
--
作者：
Eskens, FALM;Dumez, H;van Oosterom, AT
用整合素αvbeta3和alphavbeta5的抑制剂Cilengitie进行单药剂量递增I期和药代动力学研究，以确定其安全性和毒性。对于组织学或细胞学确诊的转移性实体瘤患者，西仑替丁每周两次，每小时一次，每次一小时。分别在第1天和第15天测定血浆药代动力学。37例患者纳入研究。研究剂量水平为30、60、120、180、240、400、600、850、1200和1600 mg/m(2)/次。无剂量限制性毒性(DLT)。药物动力学与剂量无关，且具有时间不变性。表观终末半衰期为3~5h。在临床前模型中，在120 mg/m(2)/次输注时，达到了最佳的抑制肿瘤生长的峰值血药浓度。使用每周两次的连续输注方案，可以安全地给予西仑替丁。由于DLT尚未达到，未来的试验应该探索不同剂量的西仑肽。(C)2003爱思唯尔科学有限公司。保留所有权利。
A single-agent dose escalating phase I and pharmacokinetic study with Cilengitide, an inhibitor of the integrins alphavbeta3 and alphavbeta5, was performed to determine its safety and toxicity. Cilengitide was administered as a one-hour infusion twice weekly without interruption to patients with histologically- or cytologically-con finned metastatic solid tumours. Plasma pharmacokinetics were determined at days I and 15. 37 patients were enrolled into the study. Dose levels studied were 30, 60, 120, 180, 240, 400, 600, 850, 1200, and 1600 mg/m(2)/infusion. There was no dose-limiting toxicity (DLT). Pharmacokinetics were dose-independent and time-invariant. Apparent terminal half-life ranged from 3 to 5 h. At 120 mg/m(2)/infusion, peak plasma concentrations were attained that optimally inhibited tumour growth in preclinical models. Cilengitide can be safely administered using a continuous twice-weekly infusion regimen. As DLT was not reached, future trials should explore Cilengitide at different doses. (C) 2003 Elsevier Science Ltd. All rights reserved.