2014年美国临床肿瘤学会年会将于当地时间5月30日～6月3日在芝加哥召开，根据大会的会议日程，我国肿瘤专家李进教授（复旦大学附属肿瘤医院肿瘤内科）在5月31日上午有一项研究在“General Poster Session”中展出，下面和大家提前分享这项精彩研究。医脉通小编们今年也将继续奔赴ASCO年会现场，及时将各项最新研究进展整理、发布，欢迎大家保持关注！

呋喹替尼（Fruquintinib）是一种新型口服小分子化合物，可以选择性抑制血管内皮生长因子受体（VEGFR）1，2，3，对多种人类肿瘤异种移植物产生强抑制作用。第一次人类1期研究发现，呋喹替尼对各种经受过多次治疗的实体瘤包括结直肠癌（CRC）患者表现出良好的耐受性和抗肿瘤活性（ORR=38.2%，CDR=82.4%）。

研究方法：

该项Ib期研究评估两种呋喹替尼治疗方案的安全性，药代动力学和疗效：每日4mg（QD）；每日5mg，维持3周，再停药1周（3/1 wk）。纳入的晚期结直肠癌患者至少2次系统性治疗失败。该项研究包含两个阶段：两组1：1随机分配到QD和3/1 wk治疗方案的阶段；选定治疗方案后的一个扩充阶段。肿瘤缓解通过RECIST 1.1进行评估。

研究结果：

在随机分配阶段有40例患者入组，QD和3/1 wk各有20例患者。两组患者的基线特征相似。QD治疗方案的中位治疗持续时间是90天（7～280天），3/1 wk方案为119天（14～364天）。治疗相关的最常见不良反应为手足综合征（HFS）、声音嘶哑、蛋白尿、高血压和疲乏。3/1 wk组发生的3～4级毒性反应事件比QD组少，尤其是手足综合征（5% vs 30%）。35例（QD组：17例，3/1wk组：18例）患者可评价治疗缓解。对于QD组，DCR=76.2%（有2例部分缓解或者PRs，2例轻微缓解或者MRs），16周无进展生存率(PFS)=40%， 9个月生存率=41.2%。在3/1wk组，DCR=83.3%（1例部分缓解，3例轻微缓解），16周无进展生存率=65.0%，9个月生存率=53.8%。3/1wk 治疗方案被选定作为推荐方案，在扩充阶段又有22例CRC患者入组。

研究结论：

研究人员认为，对于晚期结直肠癌患者给予呋喹替尼，每日5mg，以用药3周再停药1周为一个周期的治疗方案，患者表现出良好的耐受性，以及令人鼓舞的初步临床疗效。进一步的临床研究是必要的。临床试验信息：NCT01975077。

医脉通整理报道，转载请注明出处。

会议专题》》》2014年ASCO年会专题报道

阅读原文摘要

A phase 1b study of VEGFR inhibitor fruquintinib in patients with pretreated advanced colorectal cancer.（Abstract3548）

Authors: Jin Li, Junning Cao, Rui-hua Xu et al.

Session Type: General Poster Session

Background: Fruquintinib is a novel oral small molecule compound selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 with potent inhibitory effects on multiple human tumor xenografts. In the first-in-human phase I study, fruquintinib demonstrated good tolerability and impressive antitumor activity (ORR=38.2% and DCR=82.4%) in patients (pts) with various heavily pre-treated solid tumors including colorectal cancer (CRC) (ASCO 2012 Abs#3038).

Methods: This phase Ib study was designed to evaluate the safety, pharmacokinetics , and efficacy of two fruquintinib regimens: 4mg once daily continuously (QD) or 5mg once daily for three weeks followed with one week break (3/1 wk), as treatment for pts with advanced CRC who had failed at least two prior systemic therapies. The study consists of two stages: a two-arm 1:1 randomization stage including both QD and 3/1 wk regimens, and an expansion stage with the selected regimen. Tumor response was assessed per RECIST1.1. 

Results: Forty pts were enrolled in the randomization phase, with 20 pts in each QD or 3/1 wk group. Patient characteristics at baseline were similar between the two groups. The median treatment duration was 90 (7-280) days for QD regimen and 119 (14-364) days for 3/1 wk regimen. The most common treatment-related toxicities were hand-foot syndrome (HFS), hoarseness, proteinuria, hypertension and fatigue. The 3/1 wk group had less Grade 3/4 AEs than the QD group, particularly HFS (5% vs. 30%). Thirty-five pts were evaluable for response, 17 in QD and 18 in 3/1 wk. In QD group: DCR=76.2% (2 partial responses or PRs and 2 minor responses or MRs who achieved a 20-30% tumor reduction), 16-wk progression free survival (PFS)=40.0%, and 9-month survival=41.2%. In 3/1 wk group: DCR=83.3% (1 PR and 3 MRs), 16-wk PFS=65.0%, and 9-month survival=53.8%. 5mg 3/1 wk regimen was selected as the recommended regimen and additional 22 CRC pts were enrolled in the expansion stage. 

Conclusions: Fruquintinib administered at 5mg once daily in cycles of three weeks on and one week off was well tolerated and demonstrated encouraging preliminary clinical efficacy in pts with advanced CRC. Further clinical studies are warranted. Clinical trial information: NCT01975077.

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