一项评估在研口服血管生成抑制剂 motesanib 在日本晚期实体瘤患者中的安全性、耐受性、药代动力学和初步疗效的 1 期研究。

Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors.

机构信息

Division of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.

出版信息

Cancer Chemother Pharmacol. 2010 Oct;66(5):935-43. doi: 10.1007/s00280-010-1243-y. Epub 2010 Jan 28.

DOI:10.1007/s00280-010-1243-y

PMID:20107802

Abstract

PURPOSE

The aim of this study was to investigate the safety and pharmacokinetics of motesanib (AMG 706), a small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and c-Kit in Japanese patients with advanced solid tumors.

METHODS

Patients were administered motesanib orally once daily (QD) at doses of 50, 100, and 125 mg QD. The total study duration for each patient consisted of three cycles of 28 days per cycle. The primary endpoints were the incidence of dose-limiting toxicities (DLTs), estimation of the maximum tolerated dose (MTD), and assessment of pharmacokinetic parameters of motesanib.

RESULTS

Fifteen patients were enrolled and received motesanib. No DLTs were observed and, therefore, the MTD was not reached. Motesanib had acceptable toxicity at doses up to 125 mg QD. The pharmacokinetics of motesanib appears to be dose proportional. No objective responses per RECIST were observed. However, all 15 patients achieved stable disease, and five patients had durable (>24 weeks) stable disease.

CONCLUSIONS

The results of this study demonstrate that motesanib is tolerable in Japanese patients at doses up to 125 mg QD.

摘要

目的

本研究旨在探讨小分子血管内皮生长因子受体 1、2 和 3、血小板衍生生长因子受体和 c-Kit 拮抗剂 motesanib（AMG 706）在日本晚期实体瘤患者中的安全性和药代动力学。

方法

患者每日口服 motesanib 一次，剂量为 50、100 和 125 mg QD。每位患者的总研究持续时间为每 28 天为一个周期的三个周期。主要终点为剂量限制性毒性（DLT）的发生率、最大耐受剂量（MTD）的估计以及 motesanib 药代动力学参数的评估。

结果

共纳入 15 例患者接受 motesanib 治疗。未观察到 DLT，因此未达到 MTD。motesanib 在高达 125 mg QD 的剂量下具有可接受的毒性。motesanib 的药代动力学似乎呈剂量依赖性。未按 RECIST 观察到客观缓解。然而，所有 15 例患者均达到疾病稳定，5 例患者疾病稳定持续时间>24 周。