Price T J, Lipton L, McGreivy J, McCoy S, Sun Y-N, Rosenthal M A
The Queen Elizabeth Hospital, 28 Woodville Road, Woodville West, SA 5011, Australia.
Br J Cancer. 2008 Nov 4;99(9):1387-94. doi: 10.1038/sj.bjc.6604723.
The aim of this open-label phase 1b study was to assess the safety and pharmacokinetics of motesanib in combination with gemcitabine in patients with advanced solid tumours. Eligible patients with histologically or cytologically documented solid tumours or lymphoma were enroled in three sequential, dose-escalating cohorts to receive motesanib 50 mg once daily (QD), 75 mg two times daily (BID), or 125 mg QD in combination with gemcitabine (1000 mg m(-2)). The primary end point was the incidence of dose-limiting toxicities (DLTs). Twenty-six patients were enroled and received motesanib and gemcitabine. No DLTs occurred. The 75 mg BID cohort was discontinued early; therefore, 125 mg QD was the maximum target dose. Sixteen patients (62%) experienced motesanib-related adverse events, most commonly lethargy (n=6), diarrhoea (n=4), fatigue (n=3), headache (n=3), and nausea (n=3). The pharmacokinetics of motesanib and of gemcitabine were not markedly affected after combination therapy. The objective response rate was 4% (1 of 26), and 27% (7 of 26) of patients achieved stable disease. In conclusion, treatment with motesanib plus gemcitabine was well tolerated, with adverse event and pharmacokinetic profiles similar to that observed in monotherapy studies.
这项开放标签的1b期研究旨在评估莫替沙尼联合吉西他滨治疗晚期实体瘤患者的安全性和药代动力学。符合条件的组织学或细胞学确诊为实体瘤或淋巴瘤的患者被纳入三个连续的剂量递增队列，接受莫替沙尼50 mg每日一次（QD）、75 mg每日两次（BID）或125 mg QD联合吉西他滨（1000 mg m(-2)）治疗。主要终点是剂量限制性毒性（DLT）的发生率。26例患者被纳入并接受了莫替沙尼和吉西他滨治疗。未发生DLT。75 mg BID队列提前终止；因此，125 mg QD是最大目标剂量。16例患者（62%）发生了与莫替沙尼相关的不良事件，最常见的是嗜睡（n = 6）、腹泻（n = 4）、疲劳（n = 3）、头痛（n = 3）和恶心（n = 3）。联合治疗后，莫替沙尼和吉西他滨的药代动力学未受到明显影响。客观缓解率为4%（26例中的1例），27%（26例中的7例）患者病情稳定。总之，莫替沙尼加吉西他滨治疗耐受性良好，不良事件和药代动力学特征与单药治疗研究中观察到的相似。
