JCO：西地尼布治疗腺泡状软组织肉瘤效果积极

在2013年4月29日在线出版的《临床肿瘤学杂志》(Journal of Clinical Oncology)上，美国国立卫生研究院Shivaani Kummar博士等人发表了一项临床II期研究(NCT00942877)结果，该研究为目前针对转移性腺泡状软组织肉瘤(ASPS)全身性治疗方面的最大规模的前瞻性临床试验，该研究观察发现，西地尼布具有稳健的单药活性，患者ORR可达35%，在24周时的病情控制率为84%。腺泡状软组织肉瘤为一种血管丰富的罕见肿瘤类型，对于无法进行手术切除的患者，目前尚无有效的全身性标准治疗方法。而西地尼布为一种针对所有三类血管内皮生长因子受体(VEGFR)的口服型强效小分子抑制剂。

研究人员通过临床II期试验，在治疗周期为28天的研究过程中，对不能手术切除的转移性ASPS患者进行每日一次(30 mg)的西地尼布治疗，并对患者客观缓解率(ORR)进行了确定。该研究还对治疗前后活检样本的基因表达特征进行了对比，通过正电子发射断层扫描及动态增强核磁共振成像方法，评价了西地尼布对肿瘤增殖和血管生成的影响。

截至分析进行时，在招募的46例患者中，有43例患者可进行缓解评价。患者ORR为35%，在43例患者中，有15例患者取得部分缓解。26例(60%)患者病情取得稳定(最佳缓解)，在24周时的病情控制率(部分缓解+病情稳定)为84%。对来自8例患者的配对肿瘤样本进行的微阵列分析结果，以及由实时定量聚合酶链式反应进行的验证结果均表明，血管生成相关基因均出现下调。基于上述结果，目前已在进行一项非盲、多中心、随机II期注册试验，该试验主要针对转移性ASPS患者，旨在对西地尼布及另一种VEGFR抑制剂-舒尼替尼进行对比。

Cediranib for Metastatic Alveolar Soft Part Sarcoma.
PURPOSE
Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs).
PATIENTS AND METHODS
We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging.
Results
Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis.
CONCLUSION
In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib.