多西他塞联合阿西替尼对曾接受化疗的乳腺癌患者更有效

http://www.ncbi.nlm.nih.gov/pubmed/21555686

Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer.


Abstract
PURPOSE: This multicenter, randomized, double-blind, phase II study assessed safety and efficacy of axitinib plus docetaxel in metastatic breast cancer (MBC).

PATIENTS AND METHODS: Women with MBC were randomly assigned 2:1 to receive docetaxel 80 mg/m2 once every 3 weeks plus axitinib 5 mg twice per day (combination arm) or placebo (placebo arm), following a lead-in phase I trial. The primary end point was time to progression (TTP).

RESULTS: In all, 168 patients were enrolled; 112 were randomly assigned to axitinib and 56 to placebo. Median TTP was numerically longer in the combination arm than in the placebo arm (8.1 v 7.1 months), but this difference was not statistically significant (hazard ratio, 1.24; 95% CI, 0.82 to 1.87; one-sided P = .156). The difference in median TTP was greatest among patients who had received prior adjuvant chemotherapy (9.2 v 7.0 months; P = .043, prespecified subgroup analysis). Objective response rate was higher in the combination arm (41.1% v 23.6%; P = .011). The most common grades 3 to 4 treatment-related adverse events (combination/placebo) included diarrhea (10.8%/0%), fatigue (10.8%/5.4%), stomatitis (12.6%/1.8%), mucositis (9.0%/0%), asthenia (7.2%/0%), and hypertension (4.5%/0%). Three patients in the combination arm experienced serious thromboembolic events (one death). Febrile neutropenia was more frequent in the combination arm (15.3% v 7.1%); rates of other hematologic toxicities were comparable. Increased toxicity with axitinib was generally managed by dose reduction and/or growth factor support.

CONCLUSION: The addition of axitinib to docetaxel did not improve TTP in first-line MBC treatment. Combination therapy may be more effective in patients previously exposed to adjuvant chemotherapy.


这是一项随机、安慰剂对照、双盲的II期临床实验：多西他塞+阿西替尼对照多西他塞+安慰剂

多西他塞是80mg/m^2 三周方案，阿西替尼是5mg，每天两次。
结果阿西组和安慰剂组的中位无进展生存期分别是8.1个月和7.1个月，没有显著差异，但分组分析显示曾接受过辅助化疗的患者加用阿西替尼后中位无进展生存期更长，达到9.2个月，而加安慰剂的患者只有7个月，差异显著。

客观反应率方面阿西组显著高于安慰剂组，41.1% VS 23.6%。

当然阿西组的副作用更大，最常见的3级到4的与治疗相关的不良事件（阿西/安慰剂）包括腹泻（10.8% / 0%），疲劳（10.8%／5.4%），口腔炎（12.6% / 1.8%），黏膜炎（9% / 0%），乏力（7.2% / 0%），高血压（4.5% / 0%）。在阿西组有三例患者有严重的血栓栓塞事件（死亡）。发热性中性粒细胞减少在阿西组更频繁（15.3%和7.1%）。


阿西替尼更适合二线治疗。